Protein kinase Cβ inhibition attenuates osteopontin expression, macrophage recruitment, and tubulointerstitial injury in advanced experimental diabetic nephropathy

Abstract

Tubulointerstitial macrophage accumulation is an important marker of prognosis that correlates closely with declining renal function in a range of human and experimental diseases, including diabetic nephropathy. These inflammatory cells are rich in the profibrotic growth factor TGF-β such that their presence in areas of injury is frequently associated with tissue fibrosis. The migration of macrophages occurs in response to the site-specific production of chemokines, with osteopontin closely associated with their trafficking into the tubulointerstitium of the kidney. Although cell culture studies indicate that protein kinase C (FKC) mediates the expression of osteopontin, its role in the in v..