Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR‐Dependent FAK/AKT Signaling Activation

Abstract: Adverse remodeling after myocardial infarction (MI) result in heart failure and sudden cardiac death. Fibulin7 (FBLN7) is an adhesion protein excreted into the extracellular matrix that functions in multiple biological processes. However, whether and how FBLN7 affects post‐MI cardiac remodeling remains unclear. Here, the authors identify FBLN7 as a critical profibrotic regulator of adverse cardiac remodeling. They observe significantly upregulated serum FBLN7 levels in MI patients with left ventricular remodeling compared to those without MI. Microarray dataset analysis reveal FBLN7 is upregulated in human heart samples from patients with dilated and hypertrophic cardiomyopathy compared with non‐failing hearts. The authors demonstrate that FBLN7 deletion attenuated post‐MI cardiac remodeling, leading to better cardiac function and reduced myocardial fibrosis, whereas overexpression of FBLN7 results in the opposite effects. Mechanistically, FBLN7 binds to the epidermal growth factor receptor (EGFR) through its EGF‐like domain, together with the EGF‐like calcium‐binding domain, and induces EGFR autophosphorylation at tyrosine (Y) 1068 and Y1173, which activates downstream focal adhesion kinase/AKT signaling, thereby leading to fibroblast‐to‐myofibroblast transdifferentiation. In addition, FBLN7‐EGFR mediates this signal transduction, and the fibrotic response is effectively suppressed by the inhibition of EGFR activity. Taken together, FBLN7 plays an important role in cardiac remodeling and fibrosis after MI.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR‐Dependent FAK/AKT Signaling Activation ; day:21 ; month:06 ; year:2023 ; extent:15 ; Advanced science ; (21.06.2023) (gesamt 15)

Beteiligte, Orts- und Zeitangaben

• Urheber: Zheng, Xuehui ; Liu, Lingxin ; Liu, Jing ; Zhang, Chen ; Zhang, Jie ; Qi, Yan ; Xie, Lin ; Zhang, Chunmei ; Yao, Guoqing ; Bu, Peili

Weitere Informationen

• DOI: 10.1002/advs.202207631
• URN: urn:nbn:de:101:1-2023062215040491333311
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:47 MESZ