title: TGF-β signaling via TAK1 pathway: role in kidney fibrosis.
abstract: In progressive kidney diseases, fibrosis represents the common pathway to end-stage kidney failure. Transforming growth factor-β1 (TGF-β1) 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-β1 actions. Specific targeting of the TGF-β signaling pathway is seemingly critical and an attractive molecular therapeutic strategy. TGF-β1 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-β1. Importantly, recent investigations have shown that TGF-β1 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-β-activated kinase 1 and its role in mediating the profibrotic effects of TGF-β1.
authors: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mchoi@rics.bwh.harvard.edu
authors: Mary E
authors: ME
authors: Choi
authors: Yan
authors: Y
authors: Ding
authors: Sung Il
authors: SI
authors: Kim
mesh_terms: D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099151:MAP Kinase Kinase Kinase 7