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ANG II signaling and vascular fibrosis. Transforming growth factor (TGF)-β1 plays a central role in ANG II-induced vascular fibrosis. AT1R can induce TGF-β1 through an ADAM17/TNF-α pathway as well as through EGFR transactivation leading to ER stress and ROS generation. Likewise, AT1R can induce p38 activation and Arg-1 expression, both of which lead to collagen production. ANG II-induced MR activation also induces ASK1 and downstream Nox induction leading to ROS and TGF-β1 signaling.
