The gold standard for treating a heart attack—rapidly restoring blood flow—comes with a deadly catch. This sudden reoxygenation often triggers a secondary wave of tissue destruction known as ischemia/reperfusion injury. Now, a study published in Protein & Cell unveils a revolutionary strategy to neutralize this "reperfusion shock" using a recombinant protein called human MG53 (rhMG53).
For years, scientists viewed MG53 merely as a molecular "patch" that repairs damaged cell membranes. However, this new study reveals it does much more. Researchers have discovered that it also acts as a potent signaling molecule. The team demonstrated that rhMG53 actively docks onto the c-Met receptor on the surface of heart cells, entering via clathrin-mediated endocytosis.
This specific structural engagement triggers a key biological switch: the rhMG53-c-Met interaction activates the RISK and SAFE pro-survival signaling cascades, inducing a state of pharmacological preconditioning that fortifies the heart against subsequent ischemic injuryTo validate this previously unknown axis, scientists identified the protein‘s function in mouse models. Systemic delivery of rhMG53 drastically minimized cardiac tissue injury. However, when the c-Met was genetically removed or chemically blocked, the cardioprotective effects were dramatically reduced—confirming c-Met as the indispensable conduit for this therapy. Crucially, this discovery addresses key limitations in current cardiovascular pharmacotherapy. While growth factors such as HGF offer cardioprotective benefits, their clinical utility is hampered by inherent instability, high production costs, and potential cancer risks associated with long-term use. Conversely, rhMG53 demonstrates high stability, scalability for production, and intrinsic tumor-suppressive functions. Through its dual mechanism of action—mediating membrane repair and activating pro-survival signaling—rhMG53 represents a safe and promising therapeutic candidate for ischemic heart disease.

DOI：10.1093/procel/pwag022