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Indeed, NRF2 was found constitutively active in intestinal stem cell (ISC) in , and KEAP1-mediated NRF2 repression was required for ISC proliferation

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Mechanistically, Esm1 has been shown to bind to fibronectin and displace fibronectin-bound VEGF-A, thereby increasing the bioavailability and signaling capacity of the growth factor 31