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ANG II signaling in renal fibrosis. EGFR transactivation leads to ER stress, SREBP1 and TGF-β1 signaling. Likewise, ANG II signals Jnk and p38 leading to TGF-β1 induction. TGF-β1 then stimulates epithelial cell-mesenchymal cell transition. ERK and p38 both induce Smad3 signaling leading to CTGF-dependent collagen expression. ANG II-induced Rho activity also induces NF-κB leading to CTGF and HIF-1α expression.
