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Semin Nephrol. 2012 May;32(3):277-86. doi: 10.1016/j.semnephrol.2012.04.007.

Heme oxygenase-1 as a target for TGF-β in kidney disease.

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Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.


Transforming growth factor-β (TGF-β) 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-β exerts its biological functions largely via its downstream complex signaling molecules, Smad proteins. Paradoxically, TGF-β 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-β 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-β in kidney disease, its molecular regulation of HO-1 expression, and the potential role of HO-1 induction as a therapeutic modality in TGF-β-mediated kidney diseases are highlighted.

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