Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermal fibrosis, characterized by collagen accumulation, is the hallmark of several cutaneous diseases. To examine the mechanisms of collagen deposition in fibrotic skin diseases, fibroblast cultures were established from the skin of patients with progressive systemic sclerosis, morphea, scleredema, familial cutaneous collagenoma, connective tissue nevi of the collagen type, or keloids; these patients served as prototypes of fibrotic skin diseases with varying clinical features and potentially different etiologic factors. Collagen production was assayed by the synthesis of [3H]hydroxyproline, and types I and III procollagen messenger RNA (mRNA) levels were determined by dot blot hybridizations using human type I and type III procollagen-specific cDNA probes. The collagen production in fibroblast cultures from the fibrotic diseases was increased up to 6-fold over the controls, and a relatively good correlation between the collagen production and type I collagen mRNA levels was noted. The type I/III procollagen mRNA ratio in control fibroblast cultures was 5.9 +/- 1.6 (mean +/- SD). The corresponding ratio in keloid cell culture was markedly increased, while slightly decreased values were noted in the case of morphea and familial cutaneous collagenoma; the values in other cultures were within the normal range. The results suggest that procollagen production in fibroblast cultures derived from fibrotic skin diseases reflects elevated levels of the corresponding procollagen mRNA. The increased mRNA abundance, suggesting pretranslational control, may result from enhanced transcriptional activity of the corresponding gene or alternatively reflects increased stability of the mRNA molecule.
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PMID:Regulation of collagen gene expression in cutaneous diseases with dermal fibrosis: evidence for pretranslational control. 358 56

A 10-yr-old female presented with cerebriform tumors covering the plantar surfaces of both feet. Histologically, the lesions consisted of thick collagen fibers and the content of collagen per surface area of skin was increased about 8-fold. Examination of the collagen by SDS-polyacrylamide gel electrophoresis, after limited pepsin proteolysis, showed that the lesions consisted almost exclusively of type I collagen, the predominant collagen type in human skin. Thus, a diagnosis of connective tissue nevi of the collagen type was made. Fibroblast cultures were established from the affected and normal-appearing areas of the skin, and examined for the rate of collagen synthesis, production of collagenase and growth kinetics of the cells. Cell cultures derived from the lesion and from control skin synthesized procollagen at the same rate and in a normal type I/type III procollagen ratio. However, the production of enzymatically active and immunologically detectable collagenase was reduced by 70-82% in the cultures derived from the lesion as compared to controls (p less than 0.005). Fibroblasts derived from the lesions also displayed a mean population doubling time of 1.17 +/- 0.08 days compared to 1.83 +/- 0.24 and 1.92 +/- 0.09 days for control cell strains and cells derived from normal skin of the patient, respectively (p less than 0.025). These results suggest that the excessive deposition of collagen in this case may have resulted from decreased local degradation of collagen. Enhanced proliferative capacity of the regional fibroblasts may have contributed to the accumulation of collagen in these lesions.
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PMID:Decreased collagenase production by regional fibroblasts cultured from skin of a patient with connective tissue nevi of the collagen type. 627 72

Procollagen I N-proteinase (EC 3.4.24.14), the enzyme that specifically processes type I and type II procollagens to collagen, was isolated from extracts of fetal calf skin. After two chromatographic steps on concanavalin A-Sepharose and heparin-Sepharose, the semi-purified preparation was used to produce monoclonal antibodies. One reacting antibody was found to recognize not the enzyme itself but type XIV collagen on which the enzyme was bound. This binding, highly sensitive to ionic conditions (plH, salt concentrations) but not affected by non-ionic detergents, was used for affinity chromatography that strongly improved the purification procedure. The enzyme is extensively characterized: 1) it has a molecular mass of 107 kDa as determined by polyacrylamide gel electrophoresis in presence of SDS and of about 130 kDa when estimated by gel filtration on a Sephacryl-S300; 2) in standard assay (pH 7.5, 0.2 M NaCl, 35 degrees C), the activation energy for reaction with amino procollagen type I was 17,000 calories per mole. In the same conditions, Km and Vmax values were, respectively, 435 and 39 nM per hour but varied strongly with pH and salt concentration; 3) the enzyme cleaved the NH2-terminal propeptide of type I procollagen at the specific site, the Pro-Gln bond in the alpha 1 type I procollagen chain; 4) the enzyme contained a high proportion of Gly, Asx, and Glx residues but no Hyp or Hyl; 5) partial amino acid sequences obtained from internal peptides of the enzyme displayed no significant homology with known sequences. The association of procollagen I N-proteinase with a FACIT (fibril-associated collagens with interrupted triple helices) collagen as found here might be of physiological significance.
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PMID:Characterization and partial amino acid sequencing of a 107-kDa procollagen I N-proteinase purified by affinity chromatography on immobilized type XIV collagen. 762 83