articleJournal of Clinical InvestigationNov 14, 2003Closed access

Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

MSMisako SatoYMYasuteru MuragakiSSShizuya SaikaABAnita B. RobertsAOAkira Ooshima

Wakayama Medical University · National Cancer Institute · +1 more institution

Indexed incrossrefdoaj

Abstract

Tubulointerstitial fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. Transforming growth factor-β (TGF-β) is reportedly upregulated in response to injurious stimuli such as unilateral ureteral obstruction (UUO), causing renal fibrosis associated with epithelial-mesenchymal transition (EMT) of the renal tubules and synthesis of extracellular matrix. We now show that mice lacking Smad3 (Smad3ex8/ex8), a key signaling intermediate downstream of the TGF-β receptors, are protected against tubulointerstitial fibrosis following UUO as evidenced by blocking of EMT and abrogation of monocyte influx and collagen accumulation. Culture of primary renal tubular…

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Topics & keywords

Topics
Keywords
  • Fibrosis
  • Downregulation and upregulation
  • Transforming growth factor
  • Epithelial–mesenchymal transition
  • Extracellular matrix
  • Cancer research
  • Kidney
  • Signal transduction
UN Sustainable Development Goals
  • Zero hunger
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