FIZZ1 binds to B7‐H3 on fibroblasts and activates myofibroblast differentiation

Abstract

Found in inflammatory zone 1(FIZZ1) is a secreted protein involved in regulation of a wide range of biological processes, such as angiogenesis, apoptosis, cell proliferation and cell differentiation. However, its cognate receptor on target cells, such as the fibroblast, remains to be identified. To address this issue and seek out the putative receptor of FIZZ1, a FIZZ1‐AD fusion protein was constructed and used as the "bait" to screen against the mouse cDNA library fused with the BD domain in a yeast two‐hybrid system. This yielded several clones that interacted positively with the FIZZ1 bait, and which were found to contain B7‐H3, a new member of the B7 family. This FIZZ1‐B7‐H3 interaction was confirmed by co‐immunoprecipitation and FRET assays. B7‐H3 expression by fibroblasts was confirmed by immunostaining and real time PCR. Further studies indicated that FIZZ1 induced the phosphorylation of B7‐H3. In contrast to wild type fibroblasts, B7‐H3 deficient cells from knockout mice failed to undergo myofibroblast differentiation in response to FIZZ1 treatment. Taken together these data suggest that B7‐H3 may serve as the cognate receptor for FIZZ1 on fibroblasts, which mediates the downstream signaling associated with myofibroblast differentiation.Supported by NIH grants HL28737, HL31963 and HL52285.