Cellular and molecular events leading to renal tubulointerstitial fibrosis

Connective tissue remodeling of the extracellular matrix (ECM) is an essential and dynamic process associated with both physiological responses, such as wound healing, and pathological conditions, such as renal tubulointerstitial fibrosis (TIF). Data from the published literature indicate that collagens and several non-collagenous ECM glycoproteins actively contribute to TIF. The early phase of TIF is usually associated with an inflammatory process mediated by soluble factors released by activated resident cells and by infiltrating cells. Fibrogenic cytokines and growth factors secreted by inflammatory cells and fibroblasts are actively involved in connective tissue remodeling, possibly by regulating the rate of synthesis and degradation of the ECM. An uncontrolled balance of this process usually results in TIF. We review the physiology of wound healing and the pathology of fibrosis, emphasizing TIF.