Tubulointerstitial and Vascular Renal Diseases
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SMAD7 is the primary inhibitory SMAD (I-SMAD) in the TGF-β superfamily pathways. It is induced by TGF-β itself as part of a negative feedback loop. SMAD7 inhibits signaling through several mechanisms: 1) It binds to the activated Type I receptor, competing with R-SMADs (SMAD2/3) for binding and preventing their phosphorylation. 2) It recruits E3 ubiquitin ligases (like Smurf1/2) to the receptor complex, targeting it for degradation. 3) It can also interfere with the formation of the R-SMAD/SMAD4 complex. Overexpression of SMAD7 can contribute to TGF-β resistance in cancer.
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