Macrophage-myofibroblast Transition in Kidney Disease

Abstract

Abstract Increasing evidence has shown that immune cell infiltration and activation play a driving role in acute kidney injury (AKI) and chronic kidney disease (CKD) associated with progressive renal fibrosis. Macrophage-myofibroblast transition (MMT) is a newly identified cellular event involved in this process. It is well-recognized that macrophages are a major immune cell that mediates acute renal inflammation, whereas myofibroblasts are an activated form of extracellular matrix (ECM)-producing fibroblasts responsible for tissue repair (wound-healing) or fibrosis under physiological or pathological conditions. A direct link between macrophages and myofibroblasts during the progression from acute to chronic inflammation is lacking. Recent studies have revealed that macrophages play a driving role in acute to chronic inflammation via MMT. Phenotypically, MMT cells exhibit both immune and fibroblast characteristics by co-expressing monocytes/macrophages (CD68 or F4/80) and smooth muscle actin (α-SMA) markers. Moreover, MMT cells are a rich source of myofibroblasts in many chronic inflammatory diseases involving the kidneys, lungs, heart, retina, and tumor microenvironments. Mechanistically, MMT is regulated by many mediators or signaling pathways, specifically the transforming growth factor-beta (TGF-β)/ Smad3 signaling pathway. Research on the mechanisms of MMT and the development of novel therapies targeting MMT for chronic and progressive kidney diseases may present promising opportunities in medicine.