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. Author manuscript; available in PMC: 2020 Jan 29.
Published in final edited form as: Circulation. 2019 Jan 29;139(5):679–693. doi: 10.1161/CIRCULATIONAHA.118.034615

Figure 7. Model of LMO7 feedback regulation of TGF-β.

Figure 7

TGF-β signaling autoamplifies through AP-1-dependent transcriptional induction of TGFB1 and its activators, αv (ITGAV) and β3 (ITGB3) integrins. At high doses and later time points, TGF-β signaling induces expression of LMO7, which binds to and promotes the ubiquitination and degradation of AP-1 transcription factors, c-FOS and c-JUN. The resulting reduction in TGF-β activity decreases canonical SMAD3 signaling to ECM target genes including collagen, as well as cell proliferation. Positive feedback processes are indicated by green arrows, negative feedback is indicated by red arrows and lines.