TGF-β Signaling via TAK1 Pathway: Role in Kidney Fibrosis

In progressive kidney diseases, fibrosis represents the common pathway to end-stage kidney failure. Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic cytokine that has been established as a central mediator of kidney fibrosis. Emerging evidence shows a complex scheme of signaling networks that enable multifunctionality of TGF-beta 1 actions. Specific targeting of the TGF-beta signaling pathway is seemingly critical and an attractive molecular therapeutic strategy. TGF-beta 1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways involving the Smad and the non-Smad. The Smad signaling axis is known as the canonical pathway induced by TGF-beta 1. Importantly, recent investigations have shown that TGF-beta 1 also induces various non-Smad signaling pathways. In this review, we focus on current insights into the mechanism and function of the Smad-independent signaling pathway via TGF-beta-activated kinase 1 and its role in mediating the profibrotic effects of TGF-beta 1. Semin Nephrol 32:244-252 (c) 2012 Elsevier Inc. All rights reserved.