title: Increase in expression of Hsp47 and collagen in hereditary gingival fibromatosis is modulated by stress and terminal procollagen N-propeptides.
abstract: HGF is a rare oral condition characterized by a slow, progressive enlargement of the gingiva, involving both the maxilla and mandible. HGF provides a model for the study of regulatory features of conditions characterized by connective tissue hyperplasia. In this study, the culture characteristics of gingival fibroblasts derived from patients of the same family with HGF (n = 4) were similar with regard to cell cycle analysis. Flow cytometric DNA content analysis revealed uniform DNA diploidy for fibroblasts cultured from NG and HGF. NG cells showed a low S-phase fraction (19.8%) and G2/M fraction (5.8%) and a relatively high G1 phase fraction (74%). In contrast, HGF cells from all members of the tested kindred, exhibited diploid cells with a higher S-phase (40.9%) and G2/M (10.1%) fraction and a relatively low G1 phase fraction (40.9%). Furthermore, we demonstrated that the expression and production of Hsp47 parallels the increased levels of collagen secretion observed in HGF. In addition, we show that Hsp47 and collagen are coordinately regulated following stress via a feedback mechanism mediated by N-terminal procollagen propeptides. Utilizing confocal microscopy and antibodies directed against GST-fusion proteins encompassing the pro alpha1(I) N-propeptide globular domain (NP1) (residues 23-108), it was apparent that this regulatory mechanism does not involve significant interaction with Hsp47's chaperoning of procollagen.
authors.affiliation: Department of Oral Pathology, Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: R D
authors.initials: RD
authors.lastname: Coletta
authors.forename: O P
authors.initials: OP
authors.lastname: Almeida
authors.forename: L R
authors.initials: LR
authors.lastname: Ferreira
authors.forename: M A
authors.initials: MA
authors.lastname: Reynolds
authors.forename: J J
authors.initials: JJ
authors.lastname: Sauk
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005351:Fibromatosis, Gingival / Q000378:metabolism*; D030342:Genetic Diseases, Inborn / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011347:Procollagen; C494660:SERPINH1 protein, human; C047202:procollagen Type I N-terminal peptide; D003094:Collagen