Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 55 records · Page 3Linked to original sources

PubMed2001

Molecular cloning of novel mouse and human putative citrate lyase beta-subunit.

Using a fluorescent differential display (FDD) technique, a novel cDNA was identified by screening for gene expressed differentially between the Dunn osteosarcoma cell line and the LM8 cell line, an isolated variant of the Dunn cell line that has high metastatic potential to the lung. Molecular cloning of the cDNA revealed the clone has similarity to a bacterial fermentation enzyme, the citrate lyase beta-subunit (CL-beta). Northern blot and competitive reverse transcription-PCR (RT-PCR) analysis revealed up-regulation of the gene in the LM8 cell line. An RNA Master blot indicated that the mRNA encoding CL-beta is expressed abundantly in murine heart, liver, and kidney. A human expressed sequence tag (EST) database search suggested that a similar cDNA is expressed in humans. A gene with identical sequence is located on chromosome 13 in the genome database (Sanger centre, UK). These data suggest that a citrate fermentation pathway may exist in eukaryotes including mammals.

Animals↗

PubMed2001

In utero exposure to brief hyperthermia interferes with the production and migration of neocortical neurons and induces apoptotic neuronal death in the fetal mouse brain.

To investigate the pathogenetic mechanisms of brain maldevelopment induced by maternal hyperthermia, we exposed pregnant ICR mice to 43 degrees C for 12.5 min on day 13.5 or 14.5 of gestation and examined the proliferation and migration of neuronal precursor cells in the telencephalon of their fetuses. The brain weight was significantly decreased in heat-stressed fetuses when examined at 72 h after treatment. Histological examination revealed that the thickness of the neopallium, especially that of the intermediate (migratory) zone and the cortical plate, was decreased in the heated group. BrdU/anti-BrdU immunohistochemistry showed that cell proliferation in the matrix cell zone was suppressed for up to 8 h after hyperthermia and that the migration of BrdU-labeled neurons from the matrix cell zone to the primordial cortex was decelerated significantly. In addition, apoptotic cell death which is rarely observed in the brain of control animals increased in the brain of heat-stressed fetuses at 8-12 h after treatment. Thus, it seems that brief hyperthermia at critical stages of neuronal differentiation can interfere with the production and migration of neuronal precursor cells and result in abnormal brain development and neurobehavioural disturbances.

Animals↗

PubMed2001

Development of an artificial dermis preparation capable of silver sulfadiazine release.

This article describes the antibacterial effects of an artificial dermis impregnated with silver sulfadiazine (Ag-SD) in vitro as well as in vivo. In the in vitro test, silver release from the artificial dermis impregnated with Ag-SD, by immersion in collagenase solution was controlled by the degradation of the collagen sponge. The artificial dermis impregnated with 3% or higher doses of Ag-SD completely suppressed the growth of Pseudomonas aeruginosa (Ps.) or Staphylococcus aureus (St.). The cytotoxicity test revealed that impregnation of 5% or higher doses of Ag-SD suppressed the growth of fibroblasts. However, when the artificial dermis impregnated with Ag-SD was implanted into full-thickness skin defects on the backs of guinea pigs, no tissue damage was histologically observed around the implanted site of the dermis. In the in vivo test, the artificial dermis impregnated with 10% Ag-SD, which was grafted on experimentally contaminated wounds in the backs of guinea pigs, macroscopically suppressed degradation of the collagen sponge, and significantly reduced the growth of both Ps. and St., compared with artificial dermis without Ag-SD. We conclude that collagen sponge impregnated with Ag-SD is a promising artificial dermis applicable to treat contaminated wounds.

Animals↗

PubMed2001

Oxidation of phenethylamine derivatives by cytochrome P450 2D6: the issue of substrate protonation in binding and catalysis.

Cytochrome P450 (P450) 2D6 oxidizes a wide variety of drugs typically at a distance of 5-7 A from a basic nitrogen on the substrate. To investigate the determinants of P450 2D6 catalysis, we analyzed the binding and oxidation of phenethylamine substrates. P450 2D6 discriminated between the various phenethylamines, as evidenced by binding and steady-state results. Whereas the spectral binding affinity for 3-methoxyphenethylamine and 4-methoxyphenethylamine was similar, the affinity for 4-hydroxyphenethylamine was 12-fold weaker than for 3-hydroxyphenethylamine at pH 7.4. The binding of 3,4-dihydroxyphenethylamine was equally poor. These equilibrium dissociation constants were based on the observation of both type I and type II perturbation difference spectra; the former involves displacement of the proximal H(2)O ligand, yielding an iron spin state change, and the latter requires nitrogen ligation to the heme iron. One explanation for the observed type II binding spectra is the presence of both protonated and unprotonated forms of these compounds. To address this possibility, the K(S) values for 3-methoxyphenethylamine and 4-methoxyphenethylamine were determined as a function of pH. Two apparent pK(a) values were determined, which corresponded to a P450 2D6 residue involved in binding and to a lowered pK(a) of a substrate amine group upon binding P450 2D6. The apparent pK(a) of the enzyme residue (6.6) is much higher than the expected pK(a) of Asp301, which has been hypothesized to play a role in binding. Interestingly, the apparent pK(a) for the methoxyphenethylamine derivatives decreased by as much as 2 pH units upon binding to P450 2D6. 3-Methoxyphenethylamine and 4-methoxyphenethylamine underwent sequential oxidations with O-demethylation and subsequent ring hydroxylation to form 3,4-dihydroxyphenethylamine (dopamine). At higher substrate concentrations, the second oxidation was inhibited. This result can be explained by the increasing concentration of the inhibitory unprotonated substrate. Nevertheless, the rates of methoxyphenethylamine oxidations are the highest reported for P450 2D6 substrates.

Cytochrome P-450 CYP2D6↗

PubMed2001

Migration, integration, and differentiation of hippocampus-derived neurosphere cells after transplantation into injured rat spinal cord.

Hippocampus-derived neurospheres were prepared from transgenic rat fetuses expressing green fluorescent protein (GFP), and transplanted into an alginate-filled lesion of young rat spinal cord. One, two and four weeks after transplantation, a large number of grafted cells survived, many of which expressed immunoreactivity for glial fibrillary acidic protein, and a few expressed immunoreactivity for beta-tubulin III. The grafted cells closely attached to the host tissue including astrocytes at the border of the lesion. It was notable that numerous GFP-positive cells had migrated within host spinal cord tissue up to 2 mm away from the implanted site 4 weeks postoperation. These results demonstrate that rat fetal hippocampus-derived neurosphere cells could survive, differentiate, extensively migrate, and integrate well into the host spinal cord tissue.

Alginates↗

PubMed2001

Humoral immune response directed against LEDGF in patients with VKH.

Vogt-Koyanagi-Harada disease is an autoimmune systemic disorder. In Vogt-Koyanagi-Harada disease, inflammatory disorders occur in multiple organs containing melanocytes, including uvea (resulting in acute bilateral panuveitis), skin (resulting in vitiligo and alopecia), central nervous system (resulting in meningitis) and inner ears (resulting in hearing loss and tinnitus). These inflammatory aspects are attributed to the destruction of melanocytes through immunological mechanisms. Studies have been carried out to elucidate the exact etiology and target autoantigen in Vogt-Koyanagi-Harada disease, but much remains to be investigated. Identification of target autoantigen is important to understand the etiology of autoimmune diseases, and for development of antigen-specific immuno-modulation therapy. To identify the target autoantigens in Vogt-Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA expression library with serum samples obtained from patients with Vogt-Koyanagi-Harada disease. We identified an immunoreactive cDNA clone that encodes bovine lens epithelium derived growth factor. mRNA of human lens epithelium derived growth factor was determined by reverse transcription-polymerase chain reaction and it was expressed in human uvea, retina and melanocytes. Immunoglobulin G (IgG) autoantibodies were quantitated in an enzyme-linked immunosorbent assay, using recombinant human lens epithelium derived growth factor. The prevalence of IgG anti-lens epithelium derived growth factor autoantibodies in patients with Vogt-Koyanagi-Harada disease was significantly higher than that in healthy controls (66.7% versus 21.6%, P<0.001). On the other hand, the prevalence of the autoantibody in patients with panuveitis of other etiology, Behçet's disease and sarcoidosis, was almost same as that in healthy controls. These results suggest that the humoral immune response agonist lens epithelium derived growth factor is not a mere secondary phenomena caused by uveal tissue damage.

Adult↗

PubMed2001

NMR structure of the hRap1 Myb motif reveals a canonical three-helix bundle lacking the positive surface charge typical of Myb DNA-binding domains.

Mammalian telomeres are composed of long tandem arrays of double-stranded telomeric TTAGGG repeats associated with the telomeric DNA-binding proteins, TRF1 and TRF2. TRF1 and TRF2 contain a similar C-terminal Myb domain that mediates sequence-specific binding to telomeric DNA. In the budding yeast, telomeric DNA is associated with scRap1p, which has a central DNA-binding domain that contains two structurally related Myb domains connected by a long linker, an N-terminal BRCT domain, and a C-terminal RCT domain. Recently, the human ortholog of scRap1p (hRap1) was identified and shown to contain a BRCT domain and an RCT domain similar to scRap1p. However, hRap1 contained only one recognizable Myb motif in the center of the protein. Furthermore, while scRap1p binds telomeric DNA directly, hRap1 has no DNA-binding ability. Instead, hRap1 is tethered to telomeres by TRF2. Here, we have determined the solution structure of the Myb domain of hRap1 by NMR. It contains three helices maintained by a hydrophobic core. The architecture of the hRap1 Myb domain is very close to that of each of the Myb domains from TRF1, scRap1p and c-Myb. However, the electrostatic potential surface of the hRap1 Myb domain is distinguished from that of the other Myb domains. Each of the minimal DNA-binding domains, containing one Myb domain in TRF1 and two Myb domains in scRap1p and c-Myb, exhibits a positively charged broad surface that contacts closely the negatively charged backbone of DNA. By contrast, the hRap1 Myb domain shows no distinct positive surface, explaining its lack of DNA-binding activity. The hRap1 Myb domain may be a member of a second class of Myb motifs that lacks DNA-binding activity but may interact instead with other proteins. Other possible members of this class are the c-Myb R1 Myb domain and the Myb domains of ADA2 and Adf1. Thus, while the folds of all Myb domains resemble each other closely, the function of each Myb domain depends on the amino acid residues that are located on the surface of each protein.

Amino Acid Motifs↗

PubMed2001

Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities.

PURPOSE: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. METHODS AND MATERIALS: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. RESULTS: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. CONCLUSIONS: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved.

Adolescent↗

PubMed2001

Pollen tube attraction by the synergid cell.

In flowering plants, guidance of the pollen tube to the embryo sac (the haploid female gametophyte) is critical for successful fertilization. The target embryo sac may attract the pollen tube as the final step of guidance in the pistil. We show by laser cell ablation that two synergid cells adjacent to the egg cell attract the pollen tube. A single synergid cell was sufficient to generate an attraction signal, and two cells enhanced it. After fertilization, the embryo sac no longer attracts the pollen tube, despite the persistence of one synergid cell. This cessation of attraction might be involved in blocking polyspermy.

Culture Techniques↗

PubMed2001

Modified windmill porphyrin arrays: coupled light-harvesting and charge separattion, conformational relaxation in the S1 state, and S2-S2 energy transfer.

The architecture of windmill hexameric zinc(II) -porphyrin array 1 is attractive as a light-harvesting functional unit in view of its three-dimensionally extended geometry that is favorable for a large cross-section of incident light as well as for a suitable energy gradient from the peripheral porphyrins to the meso-meso-linked diporphyrin core. Three core-modified windmill porphyrin arrays 2-4 were prepared for the purpose of enhancing the intramolecular energy-transfer rate and coupling these arrays with a charge-separation functional unit. Bisphenylethynylation at the meso and meso' positions of the diporphyrin core indeed resulted in a remarkable enhancement in the intramolecular S1-S1 energy transfer in 2 with tau=2 approximately 3 ps, as revealed by femtosecond time-resolved transient absorption spectroscopy. The fluorescence lifetime of the S2 state of the peripheral porphyrin energy donor determined by the fluorescence up-conversion method was 68 fs, and thus considerably shorter than that of the reference monomer (150 fs), suggesting the presence of the intramolecular energy-transfer channel in the S2 state manifold. Such a rapid energy transfer can be understood in terms of large Coulombic interactions associated with the strong Soret transitions of the donor and acceptor. Picosecond time-resolved fluorescence spectra and transient absorption spectra revealed conformational relaxation of the S1 state of the diporphyrin core with tau = 25 ps. Upon photoexcitation of models 3 and 4, which bear a naphthalenetetracarboxylic diimide or a meso-nitrated free-base porphyrin attached to the modified diporphyrin core as an electron acceptor, a series of photochemical processes proceeded, such as the collection of the excitation energy at the diporphyrin core, the electron transfer from the S1 state of the diporphyrin to the electron acceptor, and the electron transfer from the peripheral porphyrins to the diporphyrin cation radical, which are coupled to provide a fully charge-separated state such as that in the natural photosynthetic reaction center. The overall quantum yield for the full charge separation is better in 4 than in 3 owing to the slower charge recombination associated with smaller reorganization energy of the porphyrin acceptor.

Journal Article↗

PubMed2001

Radiosensitization effect by combination with paclitaxel in vivo, including the effect on intratumor quiescent cells.

PURPOSE: To evaluate the radiosensitization effect on solid tumors upon combination treatment with paclitaxel (TXL), including the effect on intratumor quiescent (Q) cells. METHODS AND MATERIALS: Mice bearing SCC VII or EL4 solid tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days to label all proliferating (P) cells. The mice then received gamma-irradiation with or without tirapazamine (TPZ) at various time points after TXL administration. Another group of mice received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors at various time points after TXL administration. Immediately after irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, the tumor cells were isolated from the solid tumors in another group of mice, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P + Q) tumor cells were determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN or apoptosis frequency of Q cells was then used to calculate the surviving fraction of Q cells from the regression line for the relationship between the MN or apoptosis frequency and the surviving fraction of total tumor cells. RESULTS: In both SCC VII and EL4 tumors, maximum values of mitotic index (MI) and apoptosis frequency were observed 9 and 24 h after TXL administration, respectively. However, on the whole, the apoptosis frequency for SCC VII was very low. gamma-Irradiation 9 h after TXL administration induced significant radiosensitization effects on the total cells of both tumors. Irradiation at 60 h had a more significant effect on total cells of EL4 tumor, but no significant effect on total cells of SCC VII tumor. Combined treatment with TXL induced no radiosensitization effect on Q cells in either tumor. The effect on Q cells was observed only after TPZ was administered. The HF of total cells in EL4 tumors decreased significantly 60 h after TXL administration. CONCLUSION: No radiosensitization effect upon combination treatment with TXL is induced in Q tumor cells. However, the effect on P cells is produced by irradiation at the time when the maximum values of MI are induced following TXL administration. In addition, for tumors that are susceptible to apoptosis after TXL administration alone, irradiation at the time of sufficient reoxygenation in tumors after TXL administration produces a greater radioenhancement effect on P cells.

Animals↗

PubMed2001

Establishment of an expression cloning system for CD4+ T cell epitopes.

We previously reported an epitope presenting vector, pCI, a derivative of a human invariant chain (Ii) expression vector, in which the class II associated invariant chain peptide (CLIP, Ii p89-101) could be substituted with antigenic peptides. In the current study, we used this vector to develop a new expression cloning system to identify CD4+ T cell epitopes. We inserted double-stranded oligo DNAs of randomized sequences into this vector and prepared an epitope-presenting library which loads randomized 13-mer peptides onto HLA class II molecules coexpressed in COS-7 cells. Utilizing this library, we isolated a cross-reactive epitope recognized by a glutamic acid decarboxylase (GAD) 65-autoreactive T cell clone established from a patient with insulin-dependent diabetes mellitus. Although the newly identified epitope (PVQLSNQWHVVGATF) was far different from the original epitope, GAD65 p116-128 (NILLQYVVKSFDR), it did have the capacity to stimulate the T cell clone comparable to that of the original GAD epitope. Our system may be applicable not only for identifying of cross-reactive epitopes for CD4+ T cells of known specificity, but also for detection of epitopes stimulatory for CD4+ T cells the epitopes of which are unknown.

Amino Acid Sequence↗

PubMed2001

Coumarin substrates for cytochrome P450 2D6 fluorescence assays.

A set of nine 4-aminomethyl-7-alkoxycoumarin derivatives was synthesized and characterized as substrates for O-dealkylation by recombinant cytochrome P450 2D6, a major human enzyme involved in drug metabolism. Enzymatic O-dealkylation yields 7-hydroxycoumarins, which have useful fluorescence properties. The substrates, which differed in substitution at the amino and 7-hydroxy positions, varied in terms of catalytic efficiency of O-dealkylation and in their selectivity as substrates for cytochrome P450 2D6 in human liver microsomes. Several of the compounds are useful as cytochrome P450 2D6 substrates in single-phase, rapid-throughput assays.

Amino Acid Sequence↗

PubMed2001

Calcium-dependent activation of nuclear factor regulated by interleukin 3/adenovirus E4 promoter-binding protein gene expression by calcineurin/nuclear factor of activated T cells and calcium/calmodulin-dependent protein kinase signaling.

An increase in the intracellular Ca(2+) concentration controls a diverse range of cell functions, including gene expression, apoptosis, adhesion, motility, and proliferation. We have investigated Ca(2+) regulation of gene expression in rat aortic smooth muscle cells. We found that the expression of nuclear factor regulated by interleukin 3 (NFIL3)/adenovirus E4 promoter-binding protein (E4BP4)/basic region/leucine zipper (bZIP) type of a transcription factor that has a very important function in cell survival, was activated by thapsigargin (TG). This activation was inhibited by chelation of extra- or intracellular Ca(2+), suggesting that the induction by TG was dependent on the elevation of [Ca(2+)](i). Specific inhibition of calcineurin or calcium/calmodulin-dependent protein kinase (CaM kinase) by chemical means impaired the TG-induced NFIL3/E4BP4 expression. Expression of dominant negative forms of calcineurin or nuclear factor of activated T cells (NFAT) inhibited the induction of NFIL3/E4BP4 mRNA by TG. These results suggest that intracellular Ca(2+) plays a critical role in regulating gene expression of NFIL3/E4BP4 by calcineurin/NFAT and CaM kinase signaling in vascular smooth muscle cells.

Amino Acid Sequence↗

PubMed2001

p53 regulates ceramide formation by neutral sphingomyelinase through reactive oxygen species in human glioma cells.

The present study was designed to elucidate the relationship between p53 and ceramide, both of which are involved in apoptotic signaling. Treatment of human glioma cells with etoposide caused apoptosis only in cells expressing functional p53. p53 activation was followed by the formation of reactive oxygen species (ROS), superoxide anion (O2-*) measured by hydroethidium oxidation into ethidium and hydrogen peroxide (H2O2) measured by oxidation of 2',7'-dichlorofluorescin (DCFH) into 2',7'-dichlorofluorescein (DCF), which was accompanied with ceramide generation through the activation of neutral, but not acid, sphingomyelinase. Superoxide dismutase (SOD), a selective antioxidant for O2-*, had no effects on p53 expression but inhibited ceramide generation and apoptotic cell death caused by etoposide. However, catalase, a specific antioxidant for H2O2, only weakly inhibited and sodium formate, a hydroxyl radical (* OH) scavenger, unaffected etoposide-induced apoptosis. Like etoposide-induced cell death, treatment of glioma cells with the O2-*-releasing agent, pyrogallol, induced typical apoptosis and ceramide generation even in the presence of catalase. In contrast, human glioma cells lacking functional p53, either due to mutation or the expression of E6 protein of human papillomavirus, were highly resistant to etoposide and exhibited no significant change in the ceramide level. Moreover, expression of functional p53 protein in glioma cells expressing mutant p53 using a temperature-sensitive human p53(Val138) induced ceramide accumulation by the activation of neutral sphingomyelinase which was dependent on the generation of O2-*. Taken together, these results suggest that p53 may modulate ceramide generation by activation of neutral sphingomyelinase through the formation of O2-*, but not its downstream compounds H2O2 or * OH.

Apoptosis↗

PubMed2001

Gene cloning of immunogenic antigens overexpressed in pancreatic cancer.

The serological analysis of recombinant cDNA expression libraries (SEREX) by utilizing a library derived from a human pancreatic adenocarcinoma cell line and IgG antibodies from an allogeneic patient serum led to the identification of 18 genes: 13 of these were known genes, and 5 were unknown genes. In Northern and RT-PCR analyses, we found that the expression of mRNA of 14 genes was elevated in pancreatic cancer cell lines compared with the levels in normal pancreatic tissues. In addition, the expression of mRNA of hsp105 in colon cancer was greater than that in normal colon tissue. Immunohistochemical analysis using anti-hsp105 antibody revealed that an increased expression of hsp105 is a characteristic feature of pancreatic ductal and colon adenocarcinoma. Furthermore, hsp105 immunoreactivity in some cases of gastric, esophageal, and hepatocellular carcinoma was much stronger than that in normal corresponding tissues. These molecules identified may provide good diagnostic markers for cancer cells.

Actins↗

PubMed2001

Alginate, a bioresorbable material derived from brown seaweed, enhances elongation of amputated axons of spinal cord in infant rats.

Freeze-dried alginate sponge crosslinked with covalent bonds was developed in our laboratory and has been demonstrated to enhance peripheral nerve regeneration. In this study, we examined spinal cord repair using alginate sponge in infant rats. On postnatal day 8-12, the spinal cord was transversely resected at Th7-Th8 to produce a 2-mm gap. The gap was filled with alginate sponge in the alginate group. For the control group, the gap was left empty. In the alginate group, the recovery of evoked electromyogram and sensory-evoked potentials 6 weeks after surgery indicated that elongation of axons could establish electrophysiologically functional projections through the gap. A histological study revealed that myelinated and unmyelinated axons, surrounded by a perineurial-like structure, had elongated across the gap. An immunohistochemical examination revealed that elongation of astrocytic processes and/or migration of astrocytes into the alginate sponge was induced, whereas astrocyte gliosis was reduced at the interface between the implanted alginate and the host spinal cord, compared with the control group. However, a horseradish peroxidase tracing study revealed ascending and descending fibers had also elongated into the gap and reentered the other stump of the transected spinal cord beyond the gap. These results suggest that alginate might provide a permissive microenvironment for elongation of spinal cord axons.

Alginates↗

PubMed2001

Upregulation of HSP47 and collagen type III in the dermal fibrotic disease, keloid.

Keloid is a dermal fibrotic disease characterized by excessive accumulation of mainly type I collagen in extracellular matrix of the dermis. We have studied the expression levels of collagen types I and III, and its molecular chaperone HSP47 in keloid lesions and surrounding unaffected skin using Northern and Western blotting and immunohistochemical analyses. Collagen types I and III mRNA levels were found to be upregulated 20-fold in keloid tissues, contradicting previous reports of nearly normal type III collagen levels in this disease. HSP47 expression in keloid lesions was also highly upregulated; eightfold at mRNA level and more than 16-fold at the protein level. Strong upregulation of these three proteins in keloid was confirmed by immunohistochemical staining. These results suggest that accumulation of both type I and type III collagen is important for the development of keloid lesions, and that HSP47 plays a role in the rapid and extensive synthesis of collagen in keloid tissues.

Adolescent↗