Research ArticleRegenerative Medicine

Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration

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Science Translational Medicine  17 Aug 2016:
Vol. 8, Issue 352, pp. 352ra108
DOI: 10.1126/scitranslmed.aaf2304

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Drug-induced regeneration

Popping a pill to repair an organ may eventually become reality. Turning away from conventional scaffolds, materials, and cell-based regenerative medicine strategies, Fan and colleagues sought a small molecule that could specifically target a critical signaling molecule in the Hippo pathway. Loss of kinases in this pathway, MST1/2, increases cell proliferation during development; thus, the authors hypothesized that inhibiting their activity in mature organs could help repair any damage. They discovered a drug, XMU-MP-1, that blocked MST1/2 activity and found that it promoted liver repair and regeneration in four different mouse models of acute and chronic injuries, including acetaminophen-induced injury, which is a common cause of liver failure worldwide. Such a pharmacological strategy could make tissue regeneration easier for many, compared to complex biomaterial and cell therapies.