The role of hypoxia-inducible factors in renal fibrosis.

Chronic kidney disease (CKD), defined by loss of renal function, is highly prevalent, and imposes a large economic burden worldwide. Renal fibrosis is the final common pathway leading to CKD regardless of the initial insult. The extent of renal fibrosis is highly correlated with the severity of CKD. Understanding the pathophysiology of renal fibrosis is of paramount importance. Microscopically, four major pathological features are seen in renal fibrosis: interstitial extracellular matrix (ECM) deposition, cellular infiltration, tubular atrophy, and capillary rarefaction. ECM deposition may be the most prominent feature. The major components identified in fibrotic ECM are collagen type I, collagen type III, and fibronectin. In our previous study, we showed that renal pericytes/perivascular fibroblasts are the major source of scar-producing myofibroblasts in the progressively fibrotic kidney. Many argue that damaged tubular epithelial cells undergo epithelial-to-mesenchymal transition (EMT) and are responsible for renal fibrosis. However, the phenomenon of EMT was not observed in vivo in a robust model of the genetic fate-tracing technique. In line with our findings, pericytes have been identified as the major progenitors of the scar tissue in many organs including the central nervous system, colon, liver, and skin. Hypoxia-inducible factor (HIF) is a DNA-binding transcription factor activated under hypoxic conditions. It is