Research ArticleFibrosis

Selective YAP/TAZ inhibition in fibroblasts via dopamine receptor D1 agonism reverses fibrosis

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Science Translational Medicine  30 Oct 2019:
Vol. 11, Issue 516, eaau6296
DOI: 10.1126/scitranslmed.aau6296

A rewarding treatment for fibrosis

Recent data have shown that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) play an important role in fibroblast activation during fibrosis. Now, Haak et al. developed a therapeutic approach for inhibiting YAP/TAZ specifically in fibroblasts. Using rodent models, the authors found that the dopamine receptor D1 (DRD1) was selectively expressed on fibroblasts and modulated YAP/TAZ activation in the lungs. DRD1 agonists inhibited YAP/TAZ and had therapeutic effects in mouse models of lung and liver fibrosis. In lung samples from patients with pulmonary fibrosis, the enzyme responsible for dopamine synthesis was reduced, suggesting that modulating the dopaminergic pathway might be an effective strategy for treating fibrosis.

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