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Biomedical subjects

L Laitinen

Publications and source records attributed to L Laitinen.

At least 19 recordsLinked to original sources
PubMed2005

Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs.

Mesoporous silicon (PSi) microparticles were produced using thermal carbonization (TCPSi) or thermal oxidation (TOPSi) to obtain surfaces suitable for oral drug administration applications. The loading of five model drugs (antipyrine, ibuprofen, griseofulvin, ranitidine and furosemide) into the microparticles and their subsequent release behaviour were studied. Loading of drugs into TCPSi and TOPSi microparticles showed, that in addition to effects regarding the stability of the particles in the presence of aqueous or organic solvents, surface properties will affect compound affinity towards the particle. In addition to the surface properties, the chemical nature of the drug and the loading solution seems to be critical to the loading process. This was reflected in the obtained loading efficiencies, which varied between 9% and 45% with TCPSi particles. The release rate of a loaded drug from TCPSi microparticles was found to depend on the characteristic dissolution behaviour of the drug substance. When the dissolution rate of the free/unloaded drug was high, the microparticles caused a delayed release. However, with poorly dissolving drugs, the loading into the mesoporous microparticles clearly improved dissolution. In addition, pH dependency of the dissolution was reduced when the drug substance was loaded into the microparticles.

Administration, Oral↗
PubMed2003

Early clinical investigation of Viozan (sibenadet HCl), a novel D2 dopamine receptor, beta2-adrenoceptor agonist for the treatment of chronic obstructive pulmonary disease symptoms.

Viozan, (Sibenadet HCl, AR-C68397AA) is a dual D2 dopamine receptor, beta2-adrenoceptor agonist that combines bronchodilator activity with the sensory afferent modulating effects associated with D2-receptor agonism. Investigation in animal models of key chronic obstructive pulmonary disease (COPD) symptoms has demonstrated that sibenadet effectively inhibits sensory nerve activity, thereby reducing reflex cough, mucus production and tachypnoea. The results of the early clinical evaluation of this novel agent are reported. An initial proof of concept study (Study 1) aimed to determine the clinical potential of this novel agent by assessing the effects of three doses of sibenadet therapy relative to placebo, with two commonly used bronchodilators, intended to provide a benchmark against which sibenadet activity could be judged. In all, 701 patients were randomized to one of three sibenadet dose groups (400, 600 or 1000 microg ex valve), salbutamol 200 microg, ipratropium bromide (IB) 40 microg or placebo, all three times daily via pressurized metered dose inhaler (pMDI) for 4 weeks. Once the results of Study 1 had been evaluated, a dose-ranging, study (Study 2) involving 872 patients randomized to receive sibenadet (45, 270, or 495 microg ex actuator), or placebo all three times daily via pMDI, for 6 weeks commenced. Both studies were preceded by a 2-week baseline phase and followed by a 2-week follow up period.The primary efficacy variable identified changes in key COPD symptoms over the treatment period (compared with baseline data) as determined by the novel Breathlessness, Cough and Sputum Scale (BCSS). In addition, data on lung function, health-related quality of life and adverse events were collected. Patients receiving sibenadet therapy three times daily exhibited statistically significantly greater improvements in BCSS total score than those receiving placebo or bronchodilator therapy alone. A clear dose-response was evident in Study 2. Symptom improvement in this study was also accompanied by improved lung function and health-related quality of life. Sibenadet therapy was well tolerated with an adverse events profile comparable to current bronchodilator therapy. These data were viewed as extremely encouraging, warranting further, large-scale clinical investigation.

Administration, Inhalation↗
PubMed1999

Dynamic strength training in patients with early rheumatoid arthritis increases muscle strength but not bone mineral density.

OBJECTIVE: To assess the effects of 12 months' dynamic strength training on muscle strength and bone mineral density (BMD) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two subjects in the training group (EG) and 33 in the control group (CG) completed the study. EG carried out strength training 2 times a week with moderate loads of 50-70% of repetition maximum. They were also encouraged to do recreational physical activities. CG performed recreational physical activities and range of motion exercises. Maximal strength of the knee extensors, trunk extensors and flexors, and grip strength were recorded with dynamometers. BMD was measured using dual x-ray absorptiometry. Modified Disease Activity Score, erythrocyte sedimentation rate, and pain were used for the estimation of disease activity, and Stanford Health Assessment Questionnaire to measure functional disability. RESULTS: The 12 month resistance training in EG led to statistically significant mean increases of 22-35% in all muscle groups examined. CG patients were also able to increase their strength to some degree (3-24%), but at the end of the study strengths in CG were significantly lower than in EG. By the end of the study lumbar spine BMD had changed by +0.19% (4.24) in EG and by -1.14% (4.36) in CG. The corresponding changes of femoral BMD were +1.10% (3.71) and -0.03% (3.58). The changes in BMD were minor and statistically not significant in both groups. However, femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids (n = 15, 3 subjects from EG and 12 from CG) compared with changes in BMD among those not treated with systemic glucocorticoids (n = 50). CONCLUSION: Minimally supervised strength training resulted in significant improvements in muscle strength without detrimental effects on disease activity. The detected annual changes in central BMD were minor and statistically insignificant in both groups. Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment.

Arthritis, Rheumatoid↗
PubMed1997

Effects of detraining subsequent to strength training on neuromuscular function in patients with inflammatory arthritis.

The effects of detraining subsequent to strength training on neuromuscular function were examined in 39 recent-onset rheumatoid arthritis (RA) patients. Eighteen age- and sex-matched healthy people (H) served as controls. Patients were randomly allocated either to the experimental group (PE), who carried out progressive strength training for 6 months, or to the control group (PC), who maintained only their habitual physical activities. After 6 months, PE returned to their earlier physical activities and strength training was terminated. At baseline, the maximal strength of the trunk extensors (not significant), grip strength and maximal dynamic strength and the shape of the force-time curve of the knee extensors were lower in PE and PC (P < 0.05-0.001) than in H. Strength training in PE led to remarkable increases (P < 0.05-0.001) in the maximal strength of all muscle groups without changes in the shape of the force-time curve. The increases in muscle strength in PE obtained by strength training were lost to a great degree during the detraining period for the isometric trunk extension (P < 0.01) and flexion (P < 0.01) strength and for the dynamic knee extension strength (P < 0.05), but not for the grip strength. In PC, trunk extension and flexion strength decreased significantly throughout the study period. At the post-test, all the strength values in both patient groups were much lower than in H. RA is a chronic disease which seems to need continuous physical exercise with sufficient intensity to minimize/prevent the loss of muscle strength and functional capacity.

Adult↗
PubMed1996

Anchoring complex components laminin-5 and type VII collagen in intestine: association with migrating and differentiating enterocytes.

Anchoring complex component laminin-5 and its subunits laminin (Ln)-alpha3 and Ln-beta3 chains, Type VII collagen, and integrin chains alpha3, alpha6, and beta4 were studied in developing and adult human intestine and compared with findings on Ln-alpha1 and Ln-alpha2 chains. In adult human duodenum, jejunum, and ileum, Ln-5 detected with a polyclonal antiserum and Ln-alpha3 and Ln-beta3 chains, detected with monoclonal antibodies (MAbs), were restricted to the epithelial basement membranes (BMs) of villi, whereas Ln-alpha2 chain was seen only focally in crypt bottoms. In double labeling experiments, the stretch of crypt BM corresponding to the proliferative cell compartment was found to be devoid of both Ln-alpha3 and Ln-alpha2 chains. Double labeling for Ln-5 and proliferating cell nuclear antigen also showed an abrupt onset of Ln-5 expression exactly at the upper edge of the proliferative cell compartment. Type VII collagen was negligible in duodenum and showed a rising duodenal-ileal gradient localizing to villar BMs. Double labeling for Ln-5 and Type VII collagen, however, indicated only partial co-distribution in the intestine. Electron microscopy of ileum revealed both anchoring filaments and anchoring fibrils but no hemidesmosomal plaques. Our results demonstrate the expression of Ln-5 in BMs outside of stratified epithelia and indicate that Ln-5 in the intestine is associated with the compartment of migrating and differentiating enterocytes. Absence of hemidesmosomes and the presence of other anchoring complex components, such as Ln-5, Type VII collagen, and integrin chains alpha3, alpha6, and beta4, suggests unique properties for epithelial cell attachment in the intestine.

Adult↗
PubMed1995

Expression of E- and N-cadherin in renal cell carcinomas, in renal cell carcinoma cell lines in vitro and in their xenografts.

E- and N-cadherins are proteins involved in intercellular adhesion and are localized, e.g., in the adherens junctions of epithelial cells. Kidney tubules express these molecules in a distinctive pattern, the expression of N-cadherin being restricted to proximal tubules and that of E-cadherin to distal tubules and collecting ducts. Renal cell carcinomas (RCCs) and oncocytomas are considered to originate from these tubular epithelia. To find out whether cadherins could serve as markers for a cellular origin of these tumors, we studied the expression of E- and N-cadherins in RCCs and oncocytomas, in cell lines derived from RCCs as well as in tumors grown in nude mice. Most RCCs co-expressed E- and N-cadherins, as did 2 of the 4 cell lines studied. The expression pattern did not correlate with the histological grade of the tumors, and even the least differentiated tumors, as well as metastases, showed expression of cadherins. Renal oncocytomas expressed E-cadherin but not N-cadherin, which is in line with previous studies that have proposed a collecting duct origin for these tumors. Papillary renal neoplasms, a separate entity usually not classified as RCC, expressed neither of the cadherins studied despite the abundant expression of beta-catenin. Our results suggest that most RCCs co-express the characteristic adhesion molecules of both proximal and distal tubules, which makes it questionable whether the origin of these tumors can be reliably located to any distinct part of the renal tubule. Our results also suggest that in RCCs the increased histological grade is not directly associated with changes in the expression of either of the cadherins, indicating other mechanisms underlying the deficient capacity to form polarized tubular structures.

Aged↗
PubMed1995

Tenascin and fibronectin isoforms in human renal cell carcinomas, renal cell carcinoma cell lines and xenografts in nude mice.

We studied the expression of tenascin (Tn) and isoforms of fibronectin (Fn) in human renal cell carcinomas (RCC) and oncocytomas, in RCC cell lines and in their s.c. implanted xenografts in nude mice. In well-differentiated RCCs and oncocytomas extra-domain A (EDA)-Fn and Tn immunoreactivities were confined to the basement membranes and blood vessels, while in less-differentiated RCCs they were also widely seen in the stroma, correlating with the morphological differentiation of the tumor. Expression of EDB-Fn and oncofetal (onc)-Fn was very scarce in most of the RCCs and oncocytomas. Western blotting results demonstrated the predominance of the M(r) 190,000 Tn subunit in most RCCs. Among the 4 RCC cell lines, 3 showed Tn in the extracellular matrix. As xenografts, they formed moderately or poorly differentiated tumors, with abundant Tn. Three of the RCC cell lines also showed secretion of EDA-Fn and 2 of them secretion of onc-Fn and EDB-Fn into the culture medium, while in xenografts there was a strong expression of all Fn isoforms. In xenografts, the expression of Tn closely recapitulated that seen in clinical tumors and in the cell lines in vitro, while the expression of Fn isoforms in cultured cells and their xenografts was highly discordant.

Animals↗
PubMed1995

Differential expression of laminin polypeptides in developing and adult human kidney.

We studied the expression of laminin chains in embryonic and adult human kidney by indirect immunofluorescence with monoclonal antibodies (MAbs). In embryonic human kidney, immunoreactivity for laminin alpha 1, beta 1, and gamma 1 chains was found in basement membranes (BMs) of primary vesicles, in comma- and S-shaped bodies, and in more mature stages of glomeruli and in tubules. The beta 2 chain of laminin was absent in the early glomerular structures but was prominent in BMs of maturing glomeruli (GBMs) and Bowman's capsule (BCBMs) and was also detectable in some tubules. Both the beta 2 and alpha 2 chains were variably seen in medullary tubule BMs. In adult human kidney, laminin alpha 1 chain was seen in GBMs and all tubule BMs (TBMs) as well as in arterial smooth muscle BMs (SMBMs). Laminin beta 1 chain reactivity was found in all TBMs, but not in GBMs or SMBMs. In the glomerulus, a distinct mesangial type of reaction was revealed with the MAbs to beta 1 and alpha 2 chains. The GBMs and SMBMs reacted with MAbs to the beta 2 chain, but reactivity was lacking in BCBMs. Laminin gamma 1 chain immunoreactivity was weakly present in BCBMs, GBMs, and SMBMs. The alpha 3 and beta 3 chains could not be detected in developing or adult human nephron. The results show that during development the BMs in human nephron undergo distinct changes, laminin beta 1 chain being transiently co-expressed with alpha 1 chain during early glomerular development and then becoming replaced by the beta 2 chain, which, on the other hand, disappears from the BCBMs on maturation. The alpha 2 chain appears to emerge in the mesangium late during development.

Embryonic and Fetal Development↗
PubMed1995

Differential expression of laminin chains and their integrin receptors in human gastric mucosa.

The proliferating cells of the gastric mucosa are found among the pit and mucous neck cells. These cells migrate upward to renew the surface epithelium and downward to restitute the glandular cells. As the epithelial basement membranes (BMs) function as substrate for cell adhesion and migration as well as signals for their differentiation, we studied, by indirect immunofluorescence microscopy, the distribution of different laminin chains and their integrin receptors in adult human stomach. The immunoreactivity for laminin alpha 2 chain localized to the BMs of glands and the lower parts of the gastric pits whereas the laminin alpha 3 chain (laminin-5/kalinin) immunoreactivity was strictly confined to BMs underneath the surface epithelium and the upper parts of the pits. Proliferating mucosal epithelial cells, identified by Ki-67 antibodies, were confined to the areas containing both alpha 2 and alpha 3 laminin chains. The alpha 1, beta 1, and gamma 1 laminin chains were found in all BMs of the mucosa whereas the beta 2 chain was prominent in mucosal blood vessels and also detectable in some glands. Among the laminin integrin receptors, the alpha 3 and beta 4 subunits were seen to be expressed in cells along the BMs with the alpha 3 laminin chain. The alpha 6 integrin, on the other hand, was seen in all gastric epithelia. The present results demonstrate that in the adult human stomach laminin alpha 2 and alpha 3 chains show zonal distribution in BM underlying gastric mucosal epithelium whereas other laminin chains show a more general distribution.

Adult↗
PubMed1992

Integrin distributions in renal cell carcinomas of various grades of malignancy.

We studied 41 renal cell carcinomas, classified according to histologic grades G1 through G3, by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (MAb) against various integrin subunits, and the basement membrane (BM) components laminin and collagen type IV. Selected cases also were immunostained using the avidin-biotin-complex method. The alpha 3 and beta 1 integrin subunits were detected in tumor cells of all the carcinomas. All G1 carcinomas, like normal tubular epithelial cells, expressed the alpha 6 subunit, whereas it was lacking in 20% and 40% of G2 and G3 carcinomas, respectively. Furthermore, when alpha 6 was expressed, a lack of basally polarized organization of the subunit, coupled with disorganization of the BM components, correlated with histologic grade. Another feature that appeared to characterize the more anaplastic tumors was their high level (80%) of the alpha v subunit expression as compared with its absence in the G1 carcinomas. Stromal myofibroblasts, identified by double-labeling with anti-myosin, were often characterized by the expression of the alpha 1, alpha 3, alpha 5 and beta 1 subunits. These results indicate that changes in integrin expression in renal cell carcinomas may be correlated with their degree of histologic malignancy.

Basement Membrane↗
PubMed1991

Distribution of the alpha 1-alpha 6 integrin subunits in human developing and term placenta.

The distribution of the alpha 1-alpha 6 as well as alpha v, beta 1, beta 3 and beta 4 integrin subunits in human first and second trimester and term placentas was studied by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (mAbs). In first and second trimester villi, the alpha 1 and beta 1 integrin subunits were detected in the stromal cells, that were mostly also immunoreactive for desmin. Desmin-positive stromal cells were also found in villi of term placentas, but the stroma was negative for anti-alpha 1 and -beta 1. In the villous trophoblast, anti-alpha 6 and -beta 4 revealed a distinct basal immunoreactivity during all stages of development, whereas immunoreactivity for the alpha 3 and beta 1 subunits emerged during the second and third trimesters. Throughout placental development, endothelia of villous capillaries reacted prominently with anti-alpha 1 and -beta 1. Intermediate trophoblastic cells displayed a somewhat heterogenous immunoreactivity for the beta 1, alpha 1, alpha 3 and alpha 5 integrin subunits, and differed from villous trophoblast also in their lack of expression of the alpha 6 and beta 4 subunits. While nondecidualized endometrial cells displayed weak reactivity for the alpha 1 and beta 1 integrin subunits, the individual decidual cells presented both a basement membrane and a cell surface-confined immunoreactivity for anti-alpha 1, -alpha 3, and -beta 1. The results suggest a role for integrins in placental development, and show that expression of integrins is modulated during the differentiation of trophoblast, villous stroma, and decidual cells. Furthermore, the basal localization of alpha 6 beta 4 and alpha 3 beta 1 integrins suggests that they are employed as basement membrane receptors in the villous trophoblast, and the emergence of the alpha 3 beta 1 complex may reflect that the cytotrophoblast and syncytiotrophoblast recognize the basement membrane differently.

Capillaries↗
PubMed1991

Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Correlations with their functions as receptors and cell adhesion molecules.

Integrins comprise a family of transmembrane glycoproteins that modulate cell-matrix and cell-cell relationships by acting as receptors to extracellular protein ligands, and also as direct adhesion molecules. The authors studied by immunohistochemistry the distribution of the alpha 1-6,v and the beta 1,3,4 subunits of integrins in samples of normal breast, the spectrum of fibrocystic disease (FCD), and representative benign and malignant neoplasms. Monoclonal antibodies (Mabs) specific for each subunit were applied to cryosections by the avidin-biotin-complex method; selected samples were studied by double immunofluorescence microscopy with the Mabs and a polyclonal antiserum to myosin. The authors found that the alpha 1-3,6,v and the beta 1, integrin subunits were detectable in the normal breast parenchyma; myoepithelial cells were consistently more prominently stained than the basolateral aspect of the luminal cells. This immunoprofile was retained, and in cases enhanced through the spectrum of FCD, in benign tumors and in ductal and lobular carcinomas in situ. In most infiltrating ductal carcinomas, integrin staining tended to decrease except for some cases that reacted strongly for the alpha v subunit. Several mucinous carcinomas reacted strongly for alpha 2,3,6,v and beta 4 subunits, and even more so for the alpha 5 subunit that was not found in the normal breast. Subsets of infiltrating lobular carcinomas stained convincingly for alpha 1,3,6,v and beta 1 subunits in delicate but abundant kinetopodia. Our findings indicate that in hyperplasias and in benign tumors integrin expression patterns parallel those of the normal breast, whereas in carcinomas, variations include decrease, enhancement, and emergence of certain subunits that are not in the normal repertory. Alterations of integrin expression parallel phenotypic changes in breast carcinoma cells; they also reflect their disrupted interaction with the similarly disrupted extracellular matrix. Enhancement of certain integrins in some carcinomas may reflect the selection of subpopulations with increased binding capacity which in turn may impact on their invasive and metastatic properties.

Antibodies, Monoclonal↗
PubMed1991

Cellular fibronectins are differentially expressed in human fetal and adult kidney.

The localization of cellular forms of fibronectin (cFn) was studied in fetal and adult kidneys. We used monoclonal antibodies reacting with the extradomains A and B in cFN (EDAcFn, EDBcFn) as well as with a differentially glycosylated fetal form of the protein (Onc-cFn). In adult human kidney EDAcFn was present in glomerular mesangium and in the walls of larger blood vessels, whereas a polyclonal rabbit fibronectin antiserum widely reacted also with interstitial areas. Immunoreactivity for EDBcFn and Onc-cFn, however, was not found in adult kidney. In the basement membranes and interstitial areas of developing tubules and glomeruli the immunoreactivity for EDAcFn was distinct and detectable in the earlier stages also for EDBcFn. In developing glomeruli, EDAcFn and EDBcFn were detected in teh mesangial areas, but in more mature fetal glomeruli, the mesangial immunoreactivity only persisted for EDAcFn. Both EDAcFn and EDBcFn were found in the basement membranes in the medullary area of all developing kidneys. In fetal kidney, immunoreactivity for EDAcFn and EDBcFn was seen also in small blood vessels, including the capillaries. Immunoreactivity for Onc-cFn was found in mesangial cells of fetal glomeruli as well as in the intima of larger blood vessels but not in the basement membranes. The results show that the three forms of cFn are present in the fetal kidney and have certain differences in their distribution. Conversely, only the EDAcFn was detected in the adult kidney. The different, partially age-related distributions of the three types of cFns suggest that they may also differ in their functions.

Adult↗
PubMed1990

Integrins in human cells and tumors.

We have studied the distribution of the alpha- and beta-subunits of integrins in developing and adult human kidney as well as in selected other tissues and cultured cells. In cultured cells some of the integrin subunits (beta 1, alpha 1, alpha 2 and alpha 5) colocalize with talin at focal adhesions when plated on an appropriate ligand. Similarly, in tissues the polarization of beta 1-integrins in colocalization with talin appears to indicate adhesive complexes, as demonstrated in adult glomeruli. In human kidney, the alpha subunits of integrins were seen to be segment-specifically expressed already in fetal tissues. In glomeruli the integrin alpha 1 subunit characterized mesangial cells while the alpha 2 and alpha 3 subunits showed immunoreactivity in endothelial cells and podocytes, respectively. In renal tubuli, the alpha 6 subunit, complexed with the beta 1 subunit, showed a typical polarized distribution coaligning with the tubular basement membrane while the alpha 3 and alpha 2 subunits were expressed in distal tubular cells. These results suggested that in kidney the alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 integrins can function as basement membrane receptors. The alpha 5 subunit was nearly lacking in the kidney and it appears to be mainly expressed in some smooth muscle cells. In other tissues distinct patterns in the expression of integrins were found. Thus, in many glandular epithelial cells the alpha 3 beta 1 integrin appeared to function as a basement membrane receptor while in various stratified epithelia and in the breast such a polarized localization could be found for the alpha 6 beta 4 integrin. Finally, although presenting a clearly polarized distribution for beta 1 integrins, none of the alpha subunits could be found in cardiac or skeletal muscle cells and none of the integrins could be revealed in neuronal cells of human developing and adult cerebrum or cerebellum, although neurons in peripheral tissues contained abundantly the alpha 6 beta 1 integrin complex. In human tumors, the tumor cells, including also metastastatic tumors, generally presented the same integrins as their tissues of origin. In some poorly differentiated tumors both a population heterogeneity and even a lack of expression or a disorganization of basement membrane receptor integrins was obvious.

Animals↗
PubMed1990

Binding of the blood group-reactive lectins to human adult kidney specimens.

The binding of a panel of blood group-reactive lectins to frozen sections of human kidney was studied with a special emphasis on reactivity with endothelia and basement membranes. The blood group A-reactive lectins, all specific for alpha-D-N-acetylgalactosamine (GalNAc), Helix aspersa (HAA), Helix pomatia (HPA), and Griffonia simplicifolia I-A4 (GSA-I-A4) agglutinins bound to the endothelium in specimens with blood groups A and AB. In other samples, these lectins reacted predominantly with tubular basement membranes, as well as with certain tubules. Both Dolichos biflorus (DBA) and Vicia villosa agglutinins (VVA), reported to react with blood group A1 substance, failed to reveal endothelia in most specimens, but bound differently to tubules in all blood groups. The blood group B-reactive lectins, specific for alpha-D-galactose (alpha-Gal) or GalNAc, respectively, GSA-I-B4 and Sophora japonica agglutinin (SJA), bound to the endothelia in specimens from blood group B or AB and in other specimens bound only to certain tubules. Among the blood group O-reactive lectins, specific for alpha-L-fucose (Fuc), Ulex europaeus I agglutinin (UEA-I) conjugates, but not other lectins with a similar nominal specificity, bound strongly to endothelia in specimens with blood group O. The UEA-I conjugates bound distinctly more faintly to endothelia in specimens of other blood groups. The present results indicate that lectins, binding to defined blood group determinants, react with endothelia in specimens of the respective blood group status. Furthermore, they suggest that basement membranes and some tubules in the human kidney show a distinct heterogeneity in their expression of saccharide residues, related to their blood group status.

Adult↗
PubMed1990

The alpha 1-alpha 6 subunits of integrins are characteristically expressed in distinct segments of developing and adult human nephron.

We studied the distribution of the alpha 1-alpha 6 subunits of beta 1 integrins in developing and adult human kidney using a panel of mAbs in indirect immunofluorescence microscopy. Uninduced mesenchyme displayed a diffuse immunoreactivity for only the alpha 1 integrin subunit. At the S-shaped body stage of nephron development, several of the alpha subunits were characteristically expressed in distinct fetal nephron segments, and the pattern was retained also in the adult nephron. Thus, the alpha 1 subunit was characteristically expressed in mesangial and endothelial cells, the alpha 2 in glomerular endothelium and distal tubules, the alpha 3 in podocytes, Bowman's capsule, and distal tubules, and the alpha 6 subunit basally in all tubules, and only transiently in podocytes during development. Unlike the alpha 3 and alpha 6 subunits, the alpha 2 subunit displayed an overall cell surface distribution in distal tubules. It was also distinctly expressed in glomerular endothelia during glomerulogenesis. The beta 4 subunit was expressed only in fetal collecting ducts, and hence the alpha 6 subunit seems to be complexed with the beta 1 rather than beta 4 subunit in human kidney. Of the two fibronectin receptor alpha subunits, alpha 4 and alpha 5, only the latter was expressed, confined to endothelia of developing and adult blood vessels, suggesting that these receptor complexes play a minor role during nephrogenesis. The present results suggest that distinct integrins play a role during differentiation of specific nephron segments. They also indicate that alpha 3 beta 1 and alpha 6 beta 1 integrin complexes may function as basement membrane receptors in podocytes and tubular epithelial cells.

Adult↗