Activation of pericytes: recent insights into kidney fibrosis and microvascular rarefaction

Pathological deposition of fibrous matrix in organs is a major problem and contributes to as many as 45% of all natural deaths. Chronic kidney disease affects 8% of the US population, and is characterized by fibrotic processes. It frequently progresses to organ failure and is a major cause of cardiovascular death; yet it lacks therapies. Understanding the pathological mechanisms of fibrosis in the kidney and other organs is central to the development of new therapeutics.

Pericytes are mesenchymal cells that partially cover capillary walls. Pericytes play critical roles in micro-vessel formation, maturation and stability. New genetic fate-mapping studies have identified pericytes and the closely related resident fibroblasts as the major progenitors of scar-forming myofibroblasts in multiple organs including the kidney, appearing in response to tissue injury. When pericytes become myofibroblasts they lose pericyte functions. Capillaries become unstable with deleterious consequences for the kidney. The cellular and molecular mechanisms underpinning these processes are starting to unravel, leading to new therapeutics for chronic fibrosing diseases of the kidney and potentially other organs.

This review focuses on pericytes in the kidney and other organs, their role in fibrogenesis and their role in regulation of the microvasculature.