TGF-beta-activated kinase-1: New insights into the mechanism of TGF-beta signaling and kidney disease.
- Author:
Sung Il KIM
1
;
Mary E CHOI
Author Information
1. Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. mchoi@rics.bwh.harvard.edu
- Publication Type:Review
- Keywords:
Chronic kidney disease;
Fibrosis;
Intracellular signaling;
Transforming growth factor-beta1;
Transforming growth factor-beta-activated kinase 1
- MeSH:
Apoptosis;
Extracellular Matrix Proteins;
Fibrosis;
Kidney;
Kidney Diseases;
Kidney Failure, Chronic;
MAP Kinase Kinase Kinases;
Negotiating;
Phosphotransferases;
Renal Insufficiency, Chronic;
Transforming Growth Factor beta;
Transforming Growth Factor beta1;
Wound Healing
- From:Kidney Research and Clinical Practice
2012;31(2):94-105
- CountryRepublic of Korea
- Language:English
-
Abstract:
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-beta1, the prototype member of the TGF-beta superfamily, is well established as a central mediator of renal fibrosis. In chronic kidney disease, dysregulation of expression and activation of TGF-beta1 results in the relentless synthesis and accumulation of extracellular matrix proteins that lead to the development of glomerulosclerosis and tubulointerstitial fibrosis, and ultimately to end-stage renal disease. Therefore, specific targeting of the TGF-beta signaling pathway is seemingly an attractive molecular therapeutic strategy in chronic kidney disease. Accumulating evidence demonstrates that the multifunctionality of TGF-beta1 is connected with the complexity of its cell signaling networks. TGF-beta1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways. Although the Smad signaling pathway is known as a canonical pathway induced by TGF-beta1, and has been the focus of many previous reviews, importantly TGF-beta1 also induces various Smad-independent signaling pathways. In this review, we describe evidence that supports current insights into the mechanism and function of TGF-beta-activated kinase 1 (TAK1), which has emerged as a critical signaling molecule in TGF-beta-induced Smad-independent signaling pathways. We also discuss the functional role of TAK1 in mediating the profibrotic effects of TGF-beta1.
