Key result
Wild-type CD147 overexpression worsens post-TAC remodeling, cutting survival by ~21 percentage points vs vehicle.
Absolute Event Rate: 63.16% vs 84.21%
Glycosylation of CD147 promotes pathological cardiac remodeling via the TRAF2-TAK1 signaling pathway, identifying a potential interventional target for heart failure.
Glycosylation of CD147 may promote adverse remodeling in pressure overload; leaves open targeted inhibition as a heart failure therapy.
CD147, also known as EMMPRIN or basigin, is a transmembrane glycoprotein receptor that activates matrix metalloproteinases and promotes inflammation. CD147 function is regulated by posttranslational modifications of which glycosylation has attracted the most attention. In this study, we demonstrated that glycosylated CD147 was the dominant form in heart tissue, and its levels were markedly elevated in response to transverse aortic constriction (TAC). Adeno-associated virus 9-mediated, cardiac-specific overexpression of wild-type CD147 in mice significantly promoted pressure overload-induced pathological cardiac remodeling accompanied by augmented oxidative stress and ferroptosis. By contrast, mutations of CD147 glycosylation sites notably weakened these detrimental effects of CD147. Mechanistically, CD147 exacerbated TAC-induced pathological cardiac remodeling via direct binding with the adaptor molecule TRAF2 and subsequent activation of TAK1 signalling, which was dependent on glycosylation of CD147. Collectively, our findings provide the first evidence that CD147 promoted pathological cardiac remodeling and dysfunction in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signalling pathway. Thus, glycosylation of CD147 may be a potent interventional target for heart failure treatment.
No takes yet. Share an insight, caveat, or question.
Zhong et al. (2022) studied Pathological cardiac hypertrophy. AAV-9 mediated wild-type CD147 overexpression vs. Empty vector (vehicle) or AAV-9 mutant CD147 was evaluated on Survival rate at 8 weeks post-TAC. Overexpression of wild-type CD147 exacerbated pathological cardiac remodeling and reduced survival to 63.16% after TAC compared to 84.21% in vehicle, whereas mutated CD147 without glycosylation sites improved survival to 86.67%.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: