1. Isoform-selective TGF-β3 inhibition for systemic sclerosis
- Author
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Sun, Tianhe, Vander Heiden, Jason A., Gao, Xia, Yin, Jianping, Uttarwar, Salil, Liang, Wei-Ching, Jia, Guiquan, Yadav, Rajbharan, Huang, Zhiyu, Mitra, Mayurranjan, Halpern, Wendy, Bender, Hannah S., Brightbill, Hans D., Wu, Yan, Lupardus, Patrick, Ramalingam, Thirumalai, and Arron, Joseph R.
- Abstract
Transforming growth factor β (TGF-β) is implicated as a key mediator of pathological fibrosis, but its pleiotropic activity in a range of homeostatic functions presents challenges to its safe and effective therapeutic targeting. There are three isoforms of TGF-β, TGF-β1, TGF-β2, and TGF-β3, which bind to a common receptor complex composed of TGF-βR1 and TGF-βR2 to induce similar intracellular signals in vitro.We have recently shown that the cellular expression patterns and activation thresholds of TGF-β2 and TGF-β3 are distinct from those of TGF-β1 and that selective short-term TGF-β2 and TGF-β3 inhibition can attenuate fibrosis in vivowithout promoting excessive inflammation. Isoform-selective inhibition of TGF-β may therefore provide a therapeutic opportunity for patients with chronic fibrotic disorders.
- Published
- 2024
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