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Long term goal:New mechanisms and novel therapies for fibrosis The Yin & Yang and the balance of TGF-β/Smad signaling in renal fibrosis.TGF-β/Smad signaling is a key pathway leading to CKD.The imbalance of Smad signals causes tissue fibrosis.Q1.Is Smad 3 a key mediator in tissue fibrosis? Disrupted Smad3 Prevents Ana II-induced HTN.Disrupted Smad3 Prevents Ana II-Mediated renal fibrosis.