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Yoshikazu Sado

Publications and source records attributed to Yoshikazu Sado.

At least 19 recordsLinked to original sources
PubMed2006

Differential expression of basement membrane collagen-IV alpha1 to alpha6 chains during oral carcinogenesis.

This study aimed to resolve if basement membrane (BM) collagen alpha chains undergo remodeling during oral carcinogenesis. Using immunohistochemistry and transmission electron microscopy, we found that BMs in oral epithelial dysplasias (OED: mild, n=10; moderate, n=10; severe, n=10) and carcinoma in situ (CIS) (n=10) differed from normal mucosa (n=6) and oral epithelial hyperplasia (n=5) in showing: (1) excessive lamina densa-like material ultrastructurally, and (2) stronger immunoexpression for alpha5(IV) than for alpha1(IV), alpha2(IV), and alpha6(IV) chains-findings that implicate these molecules' role as an adhesive template for the attachment and persistence of basal dysplastic cells. Incipient loss of BM integrity in CIS, where alpha5(IV)/alpha6(IV) chains were more frequently absent than alpha1(IV)/alpha2(IV) chains, suggests that alpha(IV) network disruption is crucial for progression of dysplastic cells into the extracellular compartment, marking transition into the invasive phase. In carcinomatous BM, the disappearance of alpha(IV) chains was more severe in poorly differentiated oral squamous cell carcinoma (OSCC) (n=10) than in well-differentiated OSCC (n=10). In all samples examined, alpha3(IV) and alpha4(IV) chains were absent. These findings taken together suggest that BM collagen-IV alpha chains undergo remodeling where selective increase and loss of these molecules are probably early and late events, respectively, during progression of oral dysplasia to cancer.

Basement Membrane↗
PubMed2006

Tumor-specific expression of the RGD-alpha3(IV)NC1 domain suppresses endothelial tube formation and tumor growth in mice.

Angiogenesis plays an essential role in tumor growth. This study investigated expression of the noncollagenous domain of alpha3(IV) collagen (alpha3(IV)NC1) transduced into tumors and its inhibition of tumor growth. We hypothesized that if a human telomerase reverse transcriptase (hTERT) promoter-driven RGD motif containing alpha3(IV)NC1 (hTERT/RGD-alpha3(IV)NC1) were expressed in telomerase-expressing tumor cells, it would inhibit tumor growth by its anti-angiogenic property. Adenoviral transduction of hTERT/RGD-alpha3(IV)NC1 expressed RGD-alpha3(IV)NC1 in hTERT-positive tumor cell lines. However, hTERT/RGD-alpha3(IV)NC1 did not express RGD-alpha3(IV)NC1 in hTERT-negative cells such as keratinocytes and fibroblasts. The secreted RGD-alpha3(IV)NC1 in the conditioned medium from tumor cells inhibited cell proliferation as well as tube formation in cultured endothelial cells, but had no effect on other types of cells. In an in vivo model, adenoviral hTERT/RGD-alpha3(IV)NC1 gene therapy showed limited expression of RGD-alpha3(IV)NC1 in tumors and resulted in a significant decrease of vessel density in tumors. The growth of subcutaneous (s.c.) tumors in nude mice was significantly suppressed by treatment with hTERT/RGD-alpha3(IV)NC1. In addition, long-term inhibition of tumor growth was achieved by intermittent administration of hTERT/RGD-alpha3(IV)NC1. In conclusion, our findings demonstrate that tumor-specific anti-angiogenic gene therapy utilizing RGD-alpha3(IV)NC1 under the hTERT promoter inhibited angiogenesis in tumors, resulting in an antitumor effect.

Adenoviridae↗
PubMed2006

Extracellular matrix of the human cyclic corpus luteum.

Extracellular matrix regulates many cellular processes likely to be important for development and regression of corpora lutea. Therefore, we identified the types and components of the extracellular matrix of the human corpus luteum at different stages of the menstrual cycle. Two different types of extracellular matrix were identified by electron microscopy; subendothelial basal laminas and an interstitial matrix located as aggregates at irregular intervals between the non-vascular cells. No basal laminas were associated with luteal cells. At all stages, collagen type IV alpha1 and laminins alpha5, beta2 and gamma1 were localized by immunohistochemistry to subendothelial basal laminas, and collagen type IV alpha1 and laminins alpha2, alpha5, beta1 and beta2 localized in the interstitial matrix. Laminin alpha4 and beta1 chains occurred in the subendothelial basal lamina from mid-luteal stage to regression; at earlier stages, a punctate pattern of staining was observed. Therefore, human luteal subendothelial basal laminas potentially contain laminin 11 during early luteal development and, additionally, laminins 8, 9 and 10 at the mid-luteal phase. Laminin alpha1 and alpha3 chains were not detected in corpora lutea. Versican localized to the connective tissue extremities of the corpus luteum. Thus, during the formation of the human corpus luteum, remodelling of extracellular matrix does not result in basal laminas as present in the adrenal cortex or ovarian follicle. Instead, novel aggregates of interstitial matrix of collagen and laminin are deposited within the luteal parenchyma, and it remains to be seen whether this matrix is important for maintaining the luteal cell phenotype.

Collagen Type IV↗
PubMed2006

Loss of alpha3/alpha4(IV) collagen from the glomerular basement membrane induces a strain-dependent isoform switch to alpha5alpha6(IV) collagen associated with longer renal survival in Col4a3-/- Alport mice.

Mutations in COL4A3/4/5 genes that affect the normal assembly of the alpha3/4/5(IV) collagen network in the glomerular basement membrane (GBM) cause Alport syndrome. Patients progress to renal failure at variable rates that are determined by the underlying mutation and putative modifier genes. Col4a3(-/-) mice, a model for autosomal recessive Alport syndrome, progress to renal failure significantly slower on the C57BL/6 than on the 129X1/Sv background. Reported here is a novel strain-specific alternative collagen IV isoform switch that is associated with the differential renal survival in Col4a3(-/-) Alport mice. The downregulation or the absence of alpha3/4(IV) collagen chains in the GBM of Lmx1b(-/-) and Col4a3(-/-) mice was found to induce ectopic deposition of alpha5/6(IV) collagen. The GBM deposition of alpha5/6(IV) collagen was abundant in C57BL/6 Col4a3(-/-) mice but almost undetectable in 129X1/Sv Col4a3(-/-) mice. This strain difference was due to overall low expression of alpha6(IV) chain and alpha5/6(IV) protomers in the tissues of 129X1/SvJ mice, a natural Col4a6 knockdown. In (129 x B6)F1 Col4a3(-/-) mice, the amount of alpha5/6(IV) collagen in the GBM was inherited in a mother-to-son manner, suggesting that it is controlled by one or more X-linked loci, possibly Col4a6 itself. Importantly, high levels of ectopic alpha5/6(IV) collagen in the GBM were associated with approximately 46% longer renal survival. These findings suggest that alpha5/6(IV) collagen, the biologic role of which has been hitherto unknown, may partially substitute for alpha3/4/5(IV) collagen. Therapeutically induced GBM deposition of alpha5/6(IV) collagen may provide a novel strategy for delaying renal failure in patients with autosomal recessive Alport syndrome.

Animals↗
PubMed2006

Large-scale identification of genes implicated in kidney glomerulus development and function.

To advance our understanding of development, function and diseases in the kidney glomerulus, we have established and large-scale sequenced cDNA libraries from mouse glomeruli at different stages of development, resulting in a catalogue of 6053 different genes. The glomerular cDNA clones were arrayed and hybridized against a series of labeled targets from isolated glomeruli, non-glomerular kidney tissue, FACS-sorted podocytes and brain capillaries, which identified over 300 glomerular cell-enriched transcripts, some of which were further sublocalized to podocytes, mesangial cells and juxtaglomerular cells by in situ hybridization. For the earliest podocyte marker identified, Foxc2, knockout mice were used to analyze the role of this protein during glomerular development. We show that Foxc2 controls the expression of a distinct set of podocyte genes involved in podocyte differentiation and glomerular basement membrane maturation. The primary podocyte defects also cause abnormal differentiation and organization of the glomerular vascular cells. We surmise that studies on the other novel glomerulus-enriched transcripts identified in this study will provide new insight into glomerular development and pathomechanisms of disease.

Animals↗
PubMed2006

Smooth muscle trans-membrane sarcoglycan complex in partial bladder outlet obstruction.

The urinary bladder experiences both distension and contraction as a part of the normal filling and emptying cycle. To empty properly, tension generated intracellularly in a smooth muscle cell must be smoothly and efficiently transferred across its sarcolemma to the basement membrane, which mediates its binding to both the extracellular matrix and to other cells. As a consequence of urethral obstruction, the bladder cannot generate appropriate force to contract the organ, thereby leading to inefficient emptying and associated sequelae. In this study, an animal model of urethral obstruction was utilized to study the membrane-associated structures that transfer tension across the sarcolemma of bladder smooth muscle cells. Immunohistochemical localization of key components of the smooth muscle tension transfer apparatus (TTA) was performed utilizing specific antibodies against:(1) the alpha-chains of type IV collagen, a basement membrane component, and (2) beta-sarcoglycan, an integral membrane protein that is a participant in the physical linkage between the cytoskeleton and the basement membrane. We demonstrate, in obstructed animals, that there is a pronounced disruption of the TTA with a physical displacement of these two components that can be demonstrated at the level of the light microscope using scanning confocal microscopy. Electron microscopy further demonstrates significant increases in the size of the junctional plaques between smooth muscle cells.

Animals↗
PubMed2006

Immunohistochemical characterization of glomerular inflammatory cells and expression of adhesion molecules in anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses.

According to previous report, adhesion of CD8-positive cells and macrophages to glomerular endotherial cells through the lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway is crucial for the initiation and subsequent progression of anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY rats. In the present study glomerular inflammatory cell infiltration and LFA-1/ICAM-1 expression were examined in anti-GBM nephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b. The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8-positive cells after administration of IgG2a and IgG2b subclass antibodies was significantly elevated compared to that for the IgG1 subclass. The intensity of glomerular ICAM-1 immunostaining by the IgG2a and IgG2b subclass antibodies tended to be stronger than that by the IgG1 subclass. Glomerular LFA-1-positive cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than that of the IgG1 subclass. These results demonstrate that monoclonal antibodies belonging to the IgG2a and IgG2b subclasses strongly induce glomerular infiltration of inflammatory cells and expression of adhesion molecules in rat anti-GBM nephritis.

Animals↗
PubMed2006

Loss of expression of type IV collagen alpha5 and alpha6 chains in colorectal cancer associated with the hypermethylation of their promoter region.

Type IV collagen, a major component of the basement membrane (BM), is composed of six genetically distinct alpha(IV) chains, alpha1(IV) to alpha6(IV). Their genes are paired on three different chromosomes in a head-to-head arrangement. The alpha5(IV) gene (COL4A5) and the alpha6(IV) gene (COL4A6) are on chromosome Xq22 and are regulated by a bidirectional promoter. Loss of the alpha5(IV)/alpha6(IV) chains in epithelial BM occur in the early stage of cancer invasion. However, the regulatory mechanism of the specific loss of the alpha5(IV)/alpha6(IV) chains during cancer cell invasion is still undetermined. In the present study, we examined the expression of the alpha5(IV)/alpha6(IV) chains and the methylation profiles of the bidirectional promoter region of COL4A5/COL4A6 in colon cancer cell lines and colorectal tumor tissues. The expression of the alpha5(IV)/alpha6(IV) chains was down-regulated in colorectal cancer, and the loss of expression of the alpha5(IV)/alpha6(IV) chains was associated with the hypermethylation of their promoter region. In conclusion, the hypermethylation of the bidirectional promoter region of COL4A5/COL4A6 is one of the events that is responsible for the loss of expression of the alpha5(IV)/alpha6(IV) chains and the remodeling of the epithelial BM during cancer cell invasion.

Aged↗
PubMed2006

Sequential expression of type IV collagen networks: testis as a model and relevance to spermatogenesis.

The six alpha chains of type IV collagen are organized into three networks: alpha1/alpha2, alpha3/alpha4/alpha5, and alpha1/alpha2/alpha5/alpha6. A shift from the alpha1/alpha2 to the alpha3/alpha4/alpha5 network occurs in the developing glomerular basement membrane, but how the alpha1/alpha2/alpha5/alpha6 network fits into this sequence is less clear, because the three networks do not colocalize. Here, we studied the seminiferous tubule basement membrane of normal canine testis where all three networks do colocalize: the alpha1/alpha2 network is expressed from birth, the alpha1/alpha2/alpha5/alpha6 network by 5-6 weeks of age, and the alpha3/alpha4/alpha5 network by 2 months of age. A canine model of Alport syndrome allowed study of the absence of alpha3/alpha4/alpha5 and alpha1/alpha2/alpha5/alpha6 networks in testis. In Alport dogs, the seminiferous tubule basement membrane was thinner than in controls. Spermatogenesis began at the same time as with normal dogs; however, the number of mature sperm was significantly reduced in Alport dogs. Thus, it would appear that alpha3/alpha4/alpha5 and alpha1/alpha2/alpha5/alpha6 networks are not essential for onset of spermatogenesis, but long-term function may be compromised by the loss of one or both networks. This situation is analogous to the glomerular basement membrane in Alport syndrome. In conclusion, testis can serve as a model system to study the sequence of type IV collagen network expression.

Animals↗
PubMed2005

Type IV collagen induces podocytic features in bone marrow stromal stem cells in vitro.

Bone marrow-derived stromal stem cells (BMSC) can differentiate along a variety of mesenchymal lines, including mesangial cells. For determining whether BMSC can be induced to differentiate along podocytic lines in vitro, canine BMSC were cultured on plastic, type I collagen, and NC1 hexamers of type IV collagen from normal and Alport canine glomerular basement membrane. Results were compared with a mouse podocyte cell line. In the case of the podocyte line, differentiation occurred on all three matrices as indicated by the expression of synaptopodin and CD2-associated protein (CD2AP) and organization of myosin heavy chain IIA into a linear pattern. BMSC proliferated equally well on all matrices, but cells that were grown on type IV collagen NC1 hexamers became larger and stellate. Evidence for podocytic differentiation occurred on all three collagen matrices as indicated by the redistribution of myosin IIA to a linear pattern and expression of synaptopodin, CD2AP, and alpha-actinin. A punctate distribution of CD2AP was seen only in cells that were grown on normal and Alport glomerular basement membrane NC1 hexamers. Differentiated podocytes expressed the alpha1, alpha2, and alpha5 chains of type IV collagen but at higher levels in cells that were grown on NC1 hexamers. Similar results were obtained in BMSC for the alpha1 and alpha2 chains only. The alpha3, alpha4, and alpha6 chains were never detected in the podocyte line or BMSC. These results indicate that BMSC undergo a degree of podocytic differentiation in vitro and greater when grown on type IV collagen NC1 hexamers than type I collagen. Alport and normal NC1 hexamers seem equally permissive to BMSC growth and differentiation, suggesting that these processes are not influenced specifically by the alpha3/alpha4/alpha5 network. BMSC may be useful in the development of stem cell-based reconstitution of glomeruli that are damaged by disease and for gene therapy of genetic glomerular diseases such as Alport syndrome.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Immunolocalization and distribution patterns of type IV collagen alpha chains in oral mucosal melanoma.

The basement membrane (BM) is mainly composed of type IV collagen, which is composed of triple combinations of six distinct alpha (alpha) chains in a tissue-specific manner. The six collagen chain-specific antibodies (alpha1-alpha6) were used to examine the BMs of the oral epithelium (OE) and tumor clusters in oral mucosal melanoma (OMM). Eight OMM cases were examined. Results showed that the alpha1 and alpha2 chains were constantly detected at the BM of the normal OE as well as at the OE with atypical melanocytic proliferation and in invasive melanoma with nodular nests. The alpha1 and alpha2 chains were intermittently detected in in situ OMM, early invasive OMM and advanced invasive OMM with sheet-like nests. Gradual loss of alpha5 and alpha6 from the OE with atypical melanocyte through in situ OMM and early invasive OMM was observed. These findings suggest that changes in the immunolocalization and distribution patterns of type IV collagen alpha chains are associated with the progression of OMM. The distribution pattern of type IV collagen alpha chain varies depending on the architecture of the nest.

Basement Membrane↗
PubMed2005

Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy.

Members of the type IV collagen family are essential components of all basement membranes (BMs) and define structural stability as well as tissue-specific functions. The major isoform, alpha1.alpha1.alpha2(IV), contributes to the formation of many BMs and its deficiency causes embryonic lethality in mouse. We have identified an allelic series of three ENU induced dominant mouse mutants with missense mutations in the gene Col4a1 encoding the alpha1(IV) subunit chain. Two severe alleles (Bru and Svc) have mutations affecting the conserved glycine residues in the Gly-Xaa-Yaa collagen repeat. Bru heterozygous mice display defects similar to Axenfeld-Rieger anomaly, including iris defects, corneal opacity, vacuolar cataracts, significant iris/corneal adhesions, buphthalmos and optic nerve cupping, a sign indicative of glaucoma. Kidneys of Bru mice have peripheral glomerulopathy characterized by hypertrophy and hyperplasia of the parietal epithelium of Bowman's capsule. A milder allele (Raw) contains a mutation in the Yaa residue of the collagen repeat and was identified by a silvery appearance of the retinal arterioles. All phenotypes are associated with BM defects that affect the eye, kidney and other tissues. This allelic series shows that mutations affecting the collagen domain cause dominant negative effects on the expression and function of the major collagen IV isoform alpha1(IV), and pathological effects vary with the individual mutations.

Abnormalities, Multiple↗
PubMed2005

Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis.

Rapidly progressive glomerulonephritis in Goodpasture disease is mediated by autoantibodies binding to the non-collagenous NC1 domain of alpha3(IV) collagen in the glomerular basement membrane. Goodpasture epitopes in the native autoantigen are cryptic (sequestered) within the NC1 hexamers of the alpha3alpha4alpha5(IV) collagen network. The biochemical mechanism for crypticity and exposure for autoantibody binding is not known. We now report that crypticity is a feature of the quaternary structure of two distinct subsets of alpha3alpha4alpha5(IV) NC1 hexamers: autoantibody-reactive M-hexamers containing only monomer subunits and autoantibody-impenetrable D-hexamers composed of both dimer and monomer subunits. Goodpasture antibodies only breach the quaternary structure of M-hexamers, unmasking the cryptic epitopes, whereas D-hexamers are resistant to autoantibodies under native conditions. The epitopes of D-hexamers are structurally sequestered by dimer reinforcement of the quaternary complex, which represents a new molecular solution for conferring immunologic privilege to a potential autoantigen. Dissociation of non-reinforced M-alpha3alpha4alpha5(IV) hexamers by Goodpasture antibodies is a novel mechanism whereby pathogenic autoantibodies gain access to cryptic B cell epitopes. These findings provide fundamental new insights into immune privilege and the molecular mechanisms underlying the pathogenesis of human autoimmune Goodpasture disease.

Anti-Glomerular Basement Membrane Disease↗
PubMed2005

Vitamin A deficiency alters the structure and collagen IV composition of rat renal basement membranes.

Retinoids can modulate the expression of extracellular matrix (ECM) proteins with variable results depending on other contributing factors. Because changes in these proteins may alter the composition and impair the function of specialized ECM structures such as basement membranes (BMs), we studied the effects of vitamin A deficiency on renal BMs during the growing period. Newborn male rats were fed a vitamin A-deficient (VAD) diet for 50 d. The ultrastructure of renal BMs was analyzed by electron microscopy. Total collagen IV, the different alpha(IV) chains, matrix degrading metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) were quantified by immunocytochemistry and/or Western blotting. Tumor necrosis factor-alpha and interleukin-1beta were measured by ELISA. Semiquantitative RT-PCR was used for determining the steady-state levels for each alpha(IV) chain mRNA. VAD renal BMs showed an irregular thickening, particularly tubular BM. The total collagen IV content was increased, but there was a differential expression of the collagen IV chains. The protein amounts for alpha1(IV), alpha4(IV), and alpha5(IV) were similarly increased, whereas alpha2(IV) and alpha3(IV) were decreased. The levels of mRNA for each collagen IV chain changed in parallel with those of the corresponding protein. Both MMP2 and MMP9 were diminished, but no change was detected in TIMP1 or TIMP2. Our data indicate that nutritional VAD leads to alterations in the structure of renal BMs and to quantitative and qualitative variations in its collagen IV composition. These changes may be a factor predisposing to or resulting in kidney malfunction and renal disease.

Animals↗
PubMed2005

Regulation of collagen type IV genes is organ-specific: evidence from a canine model of Alport syndrome.

BACKGROUND: Despite advances in knowledge about collagen type IV at the protein level, little is known about expression of its six alpha chains. X-linked Alport syndrome provides a system to study collagen type IV gene expression within a setting of disturbed protein synthesis. Mutations in the alpha5 chain result in loss of the alpha3/alpha4/alpha5 and alpha1/alpha2/alpha5/alpha6 networks from the kidney, with progressive renal disease. METHODS: We used a canine model of Alport syndrome to measure expression of the six type IV collagen chains from 11 days to 7(1/2) months of age. We determined to what extent message levels in kidney change over time, and what correlation exists with clinical and pathologic changes in glomeruli, and the primary mutation. The latter was evaluated by examining testis, an organ normally containing the same collagen type IV networks but uninvolved by disease. RESULTS: The alpha1 to alpha6 mRNAs were expressed at all time points in normal canine kidney. By comparison to normal, in Alport dog kidney, the alpha1 and alpha2 mRNAs were up-regulated after 2 months of age, alpha3 and alpha4 mRNAs were down-regulated by 2 months of age, and the alpha5 mRNA was almost undetectable at any time. In testis, all mRNAs were expressed at comparable levels in normal and affected dogs other than the alpha5 chain, which was not expressed in affected testis. CONCLUSION: Normal expression of collagen type IV is under control mechanisms specific to each organ and to individual chains. The altered expression in canine Alport syndrome is not the direct result of the mutation, since these changes do not occur in all organs nor are they present from birth. Instead, collagen type IV expression is influenced by disease, with down-regulation of alpha3 and alpha4 chains temporally related to the onset of proteinuria, and up-regulation of alpha1 and alpha2 chains to glomerulosclerosis. This dysregulation of the alpha3 and alpha4 chains is unique to this Alport model, and suggests an unidentified mechanism linking pathology with down-regulation of expression of these two chains.

Animals↗
PubMed2004

Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats.

BACKGROUND: Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat. METHODS: GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis. CONCLUSIONS: These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.

Animals↗
PubMed2004

Differential expression of basement membrane type-IV collagen alpha1, alpha2, alpha5 and alpha6 chains among the histological subtypes of adenoid cystic carcinoma.

Six distinct alpha(IV) chains in the basement membrane (BM) of adenoid cystic carcinoma (ACC) of the salivary gland were immunohistochemically examined by anti-alpha(IV) chain-specific antibodies, and their expressions were compared with the histological subtypes and the expressions of cytokeratin 19 (CK19), cytokeratin 14 (CK14) and alpha-smooth muscle actin (alpha-SMA) and Ki-67. In the BM of normal salivary ducts, alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains were continuously stained, but alpha3(IV) and alpha4(IV) chains were negative. In the tubular and cribriform subtypes of ACC, tubules with continuous staining of alpha5(IV) and alpha6(IV) chains showed the biphasic-staining pattern among the expressions of CK19, CK14 and alpha-SMA. However, in cancer-cell nests with discontinuous or negative staining of alpha5(IV) and alpha6(IV) chains, the biphasic pattern was ambiguous. In the solid subtype, the staining of alpha1(IV) and alpha2(IV) chains was discontinuous, the staining of alpha5(IV) and alpha6(IV) chains was negative and the biphasic-staining pattern was unclear. The mitotic activity of cancer cells analyzed by the Ki-67 labeling index was significantly related to the expression of alpha5(IV) and alpha6(IV) chains in the cribriform subtype. These results suggest that BM irregularity with the differential expression of alpha(IV) chains in ACC closely relates to cell proliferation, cell differentiation and histological structure.

Adult↗