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Traf3ip2 Mediates Tweak/Tweakr-Induced Pro-Fibrotic Responses In Cultured Cardiac Fibroblasts And The Heart, Nitin A. Das, Andrea J. Carpenter, Tadashi Yoshida, Senthil A. Kumar, Sandeep Gautam, Ricardo Mostany, Reza Izadpanah, Ashok Kumar, Srinivas Mummidi, Ulrich Siebenlist, Bysani Chandrasekar

School of Medicine Publications and Presentations

Persistent inflammation promotes development and progression of heart failure (HF). TWEAK (TNF-Related WEAK Inducer Of Apoptosis), a NF-κB- and/or AP-1-responsive proinflammatory cytokine that signals via TWEAK receptor (TWEAKR), is expressed at high levels in human and preclinical models of HF. Since the adapter molecule TRAF3IP2 (TRAF3 Interacting Protein 2) is an upstream regulator of various proinflammatory pathways, including those activated by NF-κB and AP-1, we hypothesized that targeting TRAF3IP2 inhibits TWEAK-induced proinflammatory and pro-fibrotic responses in vitro and in vivo. Consistent with the hypothesis, forced expression of TRAF3IP2 upregulated TWEAK and its receptor expression in cultured adult mouse cardiac fibroblasts …