Deleting the TGF-β Receptor Attenuates Acute Proximal Tubule Injury
Year: 2012
Type: article
Abstract: TGF-β is a profibrotic growth factor in CKD, but its role in modulating the kidney's response to AKI is not well understood. The proximal tubule epithelial cell, which is the main cellular target of AKI, expresses high levels of both TGF-β and its receptors. To determine how TGF-β signaling in this tubular segment affects the response to AKI, we selectively deleted the TGF-β type II receptor in the proximal tubules of mice. This deletion attenuated renal impairment and reduced tubular apoptosis in mercuric chloride-induced injury. In vitro, deficiency of the TGF-β type II receptor protected proximal tubule epithelial cells from hydrogen peroxide-induced apoptosis, which was mediated in part by Smad-dependent signaling. Taken together, these results suggest that TGF-β signaling in the proximal tubule has a detrimental effect on the response to AKI as a result of its proapoptotic effects.
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1158069725, G1187429744, Mechanisms of EGFR Activation and Signaling in Kidney Disease, Betal Integrin and Renal Tubulogenesis, G1752511574, G209152575, Vanderbilt O'Brien Mouse Kidney Physiology and Disease Center, Cell-Matrix Interactions in the Glomerulus, G311862290, Structure Function Analysis of Integrins alpha1beta1 and alpha2beta2, Integrin/TGF-beta Axis in Tubulointerstitial Fibrosis, G5255013428, G6970558560, G7134506048, The role of the innate immune cell cyclooxygenase/prostaglandin system in blood pressureregulation
OpenAlex ID: W2136710540