Abnormal growth and clonal proliferation of fibroblasts derived from kidneys with interstitial fibrosis

Renal fibroblasts from normal kidneys (NKF cells) and from kidneys with interstitial fibrosis (FKIF cells) were established from biopsy material. In primary and passage 1 cell cultures, the amount of fibroblasts was increased by a factor of 5-10 in cultures derived from kidneys with interstitial fibrosis as compared with cultures of normal origin. As tested by clonal growth and growth kinetic experiments, FKIF cells showed significant alterations in the proliferation capacity and generation time resulting in a hyperproliferative growth in primary and secondary fibroblast cultures in vitro. Two-dimensional gel electrophoresis experiments of [35S]methionine-labeled intracellular polypeptides revealed that FKIF cells express two proteins, p53/6.1 and p48/7.5, that are not present in normal kidney and skin fibroblasts. In addition, as analyzed by two-dimensional gel electrophoresis of medium supernatants of FKIF cells, two secreted proteins specific for FKIF cells could be demonstrated. Cross-feeding experiments using conditioned medium of FKIF cells on cultures of normal human skin fibroblasts (NSF cells) revealed that FKIF cells may secrete proteins into the medium or may modify preexisting serum factors that can induce hyperproliferation in normal dermal fibroblasts. As tested by serial subcultivation and clonal analysis, FKIF cells exert significant changes in the differentiation pattern of potentially mitotic fibroblasts populations.