Heme Oxygenase-1 as a Target for TGF-beta in Kidney Disease

作者：Zarjou Abolfazl; Agarwal Anupam^*

来源：Seminars in Nephrology, 2012, 32(3): 277-286.

DOI：10.1016/j.semnephrol.2012.04.007

• Transforming growth factor-beta
• heme oxygenase-1
• kidney injury
• fibrosis

Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory cytokine that is implicated in a variety of kidney diseases, including diabetic nephropathy and chronic transplant rejection, where it promotes stimulation of the extracellular matrix deposition, cell proliferation, and migration. TGF-beta exerts its biological functions largely via its downstream complex signaling molecules, Smad proteins. Paradoxically, TGF-beta also is essential for normal homeostasis and suppression of inflammation through mechanisms that are yet to be fully elucidated. One feasible mechanism by which TGF-beta may exert its beneficial properties is through induction of heme oxygenase-1 (HO-1). Induction of this redox-sensitive enzyme is known to be cytoprotective through its potent antioxidant, anti-inflammatory, and anti-apoptotic properties in different conditions including several kidney diseases. In this overview, recent advances in our understanding of the role of TGF-beta in kidney disease, its molecular regulation of HO-1 expression, and the potential role of HO-1 induction as a therapeutic modality in TGF-beta-mediated kidney diseases are highlighted.

• 出版日期2012-5