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FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.
Hwang, Hyun Jung; Kang, Donghee; Kim, Jae-Ryong; Choi, Joon Hyuk; Ryu, Ji-Kan; Herman, Allison B; Ko, Young-Gyu; Park, Heon Joo; Gorospe, Myriam; Lee, Jae-Seon.
Afiliación
  • Hwang HJ; Research Center for Controlling Intercellular Communication and.
  • Kang D; Department of Molecular Medicine, College of Medicine, Inha University, Incheon, Korea.
  • Kim JR; Research Center for Controlling Intercellular Communication and.
  • Choi JH; Department of Molecular Medicine, College of Medicine, Inha University, Incheon, Korea.
  • Ryu JK; Program in Biomedical Science and Engineering, Inha University, Incheon, Korea.
  • Herman AB; Department of Biochemistry and Molecular Biology and.
  • Ko YG; Department of Pathology, College of Medicine, Yeungnam University, Daegu, Korea.
  • Park HJ; Research Center for Controlling Intercellular Communication and.
  • Gorospe M; Department of Urology, College of Medicine, Inha University, Incheon, Korea.
  • Lee JS; Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, NIH, Baltimore, Maryland, USA.
JCI Insight ; 9(7)2024 Apr 08.
Article en En | MEDLINE | ID: mdl-38587072
ABSTRACT
The roles of fibronectin leucine-rich transmembrane protein 2 (FLRT2) in physiological and pathological processes are not well known. Here, we identify a potentially novel function of FLRT2 in preventing endothelial cell senescence and vascular aging. We found that FLRT2 expression was lower in cultured senescent endothelial cells as well as in aged rat and human vascular tissues. FLRT2 mediated endothelial cell senescence via the mTOR complex 2, AKT, and p53 signaling pathway in human endothelial cells. We uncovered that FLRT2 directly associated with integrin subunit beta 4 (ITGB4) and thereby promoted ITGB4 phosphorylation, while inhibition of ITGB4 substantially mitigated the induction of senescence triggered by FLRT2 depletion. Importantly, FLRT2 silencing in mice promoted vascular aging, and overexpression of FLRT2 rescued a premature vascular aging phenotype. Therefore, we propose that FLRT2 could be targeted therapeutically to prevent senescence-associated vascular aging.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Células Endoteliales Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Células Endoteliales Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos