Analysis of pathological activities of CCN proteins in fibrotic diseases: Kidney fibrosis

Abstract

Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis. Transforming growth factor-β (TGF-β) is postulated to play a role in the development of both fibrotic processes. Extracellular matrix proteins, particularly type I collagen and fibronectin, accumulate in the tissue during renal fibrogenesis. CCN2, also known as connective tissue growth factor (CTGF), is increased in the setting of fibrosis and modulates a number of downstream signaling pathways involved in the fibrogenic properties of TGF-β. Unilateral ureteral obstruction is one of the most widely used models of renal tubulointerstitial fibrosis. Herein, we describe unilateral ureteral obstruction in mice as an animal model of renal fibrosis and methods for immunohistochemical analyses of extracellular matrix proteins and CCN2. In addition, we describe the construction of podocyte-specific CCN2-transgenic mice for analyzing mesangial matrix expansion and glomerulosclerosis.