Hyperglycemia activates FGFR1

Cardiomyocytes Diabetic cardiomyopathy FGFR1 Inflammatory responses NFκB Protein tyrosine kinases Toll-like receptor 4 c-Src

Journal

Acta pharmaceutica Sinica. B
ISSN: 2211-3835
Titre abrégé: Acta Pharm Sin B
Pays: Netherlands
ID NLM: 101600560

Informations de publication

Date de publication:
Apr 2024
Historique:
received: 29 09 2023
revised: 11 12 2023
accepted: 05 01 2024
medline: 4 4 2024
pubmed: 4 4 2024
entrez: 4 4 2024
Statut: ppublish

Résumé

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses

Identifiants

DOI: 10.1016/j.apsb.2024.01.013 PMID: 38572108 PMC: PMC10985127
pubmed: 38572108
doi: 10.1016/j.apsb.2024.01.013
pii: S2211-3835(24)00016-9
pmc: PMC10985127
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1693-1710

Informations de copyright

© 2024 The Authors.

Déclaration de conflit d'intérêts

The authors declare no conflicts of interest.

Auteurs

Xiong Chen (X)

Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Department of Wound Repair, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Jinfu Qian (J)

Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Shiqi Liang (S)

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Jianchang Qian (J)

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

Wu Luo (W)

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

Yujuan Shi (Y)

Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

Hong Zhu (H)

Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Xiang Hu (X)

Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Gaojun Wu (G)

Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Xiaokun Li (X)

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Department of Wound Repair, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.

Guang Liang (G)

Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou 311399, China.

Classifications MeSH