English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Tubulointerstitial injury leading to fibrosis is a common pathway of many renal diseases. During this type of injury, modeled by unilateral ureteral obstruction (UUO), cells undergo epithelial-to-mesenchymal transition (EMT), a process that is mediated by various cytokines that modulate the biology of extracellular matrix proteins. Here, we studied the tubulointerstitial nephritis antigen (TINag), a tubular basement membrane protein, in the UUO model of tubulointerstitial injury. We observed upregulation of type IV collagen but downregulation of both laminin and TINag in obstructed kidneys. TINag downregulation was a result of oxidative stress; in the proximal tubular epithelial cell line HK-2, TINag expression and its promoter activity decreased after treatment with H2O2. We identified multiple CCAAT/enhancer binding protein beta (C/EBP-beta) motifs in the TINag promoter and observed that oxidant stress perturbed interactions between TINag DNA and C/EBP-beta protein. Oxidant stress reduced nuclear translocation of C/EBP-beta in HK-2 cells, which was restored by antioxidants. In addition, overexpression of C/EBP-beta restored the H2O2-induced reduction of TINag promoter activity and expression. Furthermore, in vivo, renal obstruction reduced nuclear expression of C/EBP-beta. Cells grown on a TINag substratum maintained their normal epithelial phenotype and cytoskeletal organization, similar to those grown on type IV collagen, and demonstrated reduced synthesis of fibronectin. Taken together, these findings suggest that altered interactions between C/EBP-beta and TINag play a critical role in the pathophysiology of renal injury after obstruction.

C/EBP-β Modulates Transcription of Tubulointerstitial Nephritis Antigen in Obstructive Uropathy