The role of interstitial cells in the progression of renal diseases

Abstract

Renal interstitial fibrosis (RIF) is frequently associated with distinct inflammatory and noninflammatory glomerular diseases. RIF is mainly responsible for a decline of excretory renal function and therefore influences the prognosis of several renal diseases. The resident interstitial cells of the kidney, which play a major role in causing RIF, are different renal fibroblasts, which respond to a variety of cytokines released by various cell types. Immunohistochemical analysis of human renal biopsies with different glomerulopathies revealed that CD2+ T lymphocytes are the major cells infiltrating the renal interstitium. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/HLA-DP antigens, often associated with an aberrant expression of the intercellular adhesion molecule 1, was observed on proximal tubular epithelial cells, indicating that these cells may play an important role in local immune responses and probably function as antigen-presenting cells. Furthermore, it has been shown by Northern blot analysis that renal epithelial cells in culture express interleukin 6, platelet-derived growth factor and granulocyte-macrophage colony stimulating factor. Cell cultures established from renal biopsies revealed the presence of the three mitotic fibroblast types (MF I through MF III) and the three postmitotic types (PMF IV through PMF VI). The frequencies of the various progenitor fibroblasts MF I, MF II, and MF III differed significantly in cultures established from kidneys with (FKIF cells) and without RIF (NKF cells). In comparison to NKF cells, FKIF cells are characterized by the expression of a "new" protein, called "FIBROSIN," which seems to be specific for FKIF cells. Furthermore, FKIF cells showed a hyperproliferative growth pattern and produced elevated amounts of extracellular matrix, especially of the collagen types III and V. Further extended analyses are currently performed in order to clarify the interrelationships between infiltrating and resident interstitial cells on one side, and renal epithelial/endothelial and resident interstitial cells on the other side that may be involved in the pathogenesis of RIF.