Increase in expression of Hsp47 and collagen in hereditary gingival fibromatosis is modulated by stress and terminal procollagen N-propeptides

HGF is a rare oral condition characterized by a slow, progressive enlargeme nt of the gingiva, involving both the maxilla and mandible. HGF provides a model for the study of regulatory features of conditions characterized by c onnective 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 c ontent analysis revealed uniform DNA diploidy for fibroblasts cultured from NG and HGF. NG cells showed a low S-phase fraction (19.8%) and G(2)/M frac tion (5.8%) and a relatively high G(1) phase fraction (74%), In contrast, H GF cells from all members of the tested kindred, exhibited diploid cells wi th 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 secreti on observed in HGF. In addition, we show that Hsp47 and collagen are coordi nately regulated following stress via a feedback mechanism mediated by N-te rminal procollagen propeptides. Utilizing confocal microscopy and antibodie s directed against GST-fusion proteins encompassing the pro alpha 1(I) N-pr opeptide globular domain (NP1) (residues 23-108), it was apparent that this regulatory mechanism does not involve significant interaction with Hsp47's chaperoning of procollagen.