Abstract
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.
Highlights
Heart failure (HF) is a common final stage of many cardiovascular diseases and is characterised by functional impairment of ventricular filling or ejection [1]
Our results demonstrated that CD147 overexpression significantly promoted transverse aortic constriction (TAC)-induced cardiac remodeling, while glycosylation site mutagenesis notably weakened the detrimental effects of CD147 via suppression of CD147-TRAF2 binding and downstream activation of TAK1 signalling
We evaluated whether the expression of CD147 and its glycosylation levels were altered in the pressure overload-induced hypertrophic model
Summary
Heart failure (HF) is a common final stage of many cardiovascular diseases and is characterised by functional impairment of ventricular filling or ejection [1]. Pathological cardiac hypertrophy and adverse ventricular remodeling in response to various extracellular stress stimuli are fundamental morphological changes during the progression of HF [3]. It is important to identify molecular regulators of pathological cardiac hypertrophy and discover novel therapeutic targets. Cluster of differentiation (CD) 147 ( known as EMMPRIN and basigin) is encoded by the BSG gene and is a versatile transmembrane glycoprotein that promotes matrix metalloproteinase (MMP) activation, myofibroblast differentiation, fibrosis, and oxidative stress [5, 6]. Recent reports have demonstrated that CD147 is involved in the development and progression of cardiovascular diseases, including ischemic cardiomyopathy [8, 9], heart failure [10], and atherosclerosis [11]. Highly glycosylated but not low-glycosylated CD147 plays a crucial role in MMP induc-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
