Oncostatin M promotes versican expression in cardiac fibroblasts to facilitate extracellular matrix remodeling

Myocardial injury is accompanied by an acute inflammatory response. Our previous work identified Oncostatin M as a key cytokine promoting heart regeneration through stimulating cardiomyocyte proliferation, while its effects on fibroblasts cannot be ignored. Cytokines are generally recognized to activate profibrotic gene programs in cardiac fibroblasts, a process traditionally regarded as detrimental to functional repair. Here, we showed that OSM enhanced cardiac fibroblasts to express versican, a pro-regenerative ECM component in the heart, through activating gp130/JAK/STAT3 signaling pathway. We determined that OSM steered fibroblasts toward a pro-regenerative state by promoting regenerative extracellular matrix remodeling.