Renal fibrosis is characterized by excessive deposition of extracellular matrix (ECM), leading to destruction of normal kidney architecture and loss of renal function. The activation of α-smooth muscle actin-positive myofibroblasts plays a key role in this process. After kidney injury, profibrotic factors are secreted by injured tubular epithelia and infiltrated inflammatory cells to promote complex cascades of signaling events leading to myofibroblastic activation, proliferation, and ECM production. The origins of myofibroblasts remain controversial, and possibilities include resident fibroblasts, pericytes, bone marrow-derived cells, and endothelial cells. Recent evidence supports the existence of localized fibrogenic niches, which provides a specialized tissue microenvironment for myofibroblastic activation and expansion. Myofibroblasts often undergo epigenetic modifications, leading to their sustained activation and resistance to apoptosis. In this chapter, we discuss the origins, heterogeneity, and activation of myofibroblasts in diseased kidneys. We also highlight novel strategies for the treatment of patients with fibrotic kidney diseases.
Keywords: EMT; Fibrotic niche; Myofibroblast; Renal fibrosis; Wnt signaling.