The progression of renal diseases: On the pathogenesis of renal interstitial fibrosis

Abstract

Renal interstitial fibrosis (RIF) frequently occurs in inflammatory and non-inflammatory kidney diseases and is associated with a decline in renal excretory function. Fibroblasts which occupy the renal interstitium are involved mainly in the formation of RIF not only by the production of extracellular matrix, but also by regulatory processes. They respond to a variety of cytokines released by different cell types. To investigate mechanisms leading to RIF, immunohistochemical analysis and cell cultures of renal biopsies in various renal diseases have been performed. T lymphocytes are the major cells infiltrating the renal interstitium, and their number correlates with the impairment of renal function. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/-DP molecules, frequently associated with an aberrant expression of the intercellular adhesion molecule 1 (ICAM-1), was observed on proximal tubular epithelial cells, indicating that these cells may play a role in antigen presentation. The cell biological experiments revealed the presence of the three mitotic fibroblast types (MFI-MFIII) and the three postmitotic types (PMFIV-PMFVI) in the cell culture. The number of fibroblasts in primary and passage-1 culture was increased sevenfold in cultures derived from kidneys with RIF (FKIF cells) in comparison to normal kidneys (NKF cells). FKIF cells show hyperproliferative growth and synthesize an increased amount of total collagen, especially types III and V. These cells express a protein, named “FIBROSIN”, which seems to be specific for FKIF cells. Further extended cell biological analyses are currently being performed to investigate interactions of tubular cells, lymphocytes, macrophages, and fibroblasts in order to shed more light on the pathomechanisms involved in fibrogenesis leading to renal interstitial fibrosis.