bFGF alleviates diabetes-associated endothelial impairment by downregulating inflammation via S-nitrosylation pathway

Abstract

Protein S-nitrosylation is a reversible protein modification implicated in both physiological and pathophysiological regulation of protein function. However, the relationship between dysregulated S-nitrosylation homeostasis and diabetic vascular complications remains incompletely understood. Here, we demonstrate that basic fibroblast growth factor (bFGF) is a key regulatory link between S-nitrosylation homeostasis and inflammation, and alleviated endothelial dysfunction and angiogenic defects in diabetes. Subjecting human umbilical vein endothelial cells (HUVECs) to hyperglycemia and hyperlipidemia significantly decreased endogenous S -nitrosylated proteins, including S-nitrosylation of inhibitor kappa B kinase β (IKKβ C179 ) and transcription factor p65 (p65 C38 ), which was alleviated by bFGF co-treatment. Pretreatment with carboxy-PTIO (c-PTIO), a nitric oxide scavenger, abolished bFGF-mediated S-nitrosylation increase and endothelial protection. Meanwhile, nitrosylation-resistant IKKβ C179S and p65 C38S mutants exacerbated endothelial dysfunction in db/db mice, and in cultured HUVECs subjected to hyperglycemia and hyperlipidemia. Mechanistically, bFGF-mediated increase of S-nitrosylated IKKβ and p65 was attributed to synergistic effects of increased endothelial nitric oxide synthase (eNOS) and thioredoxin (Trx) activity. Taken together, the endothelial protective effect of bFGF under hyperglycemia and hyperlipidemia can be partially attributed to its role in suppressing inflammation via the S-nitrosylation pathway.

Novel Thermosensitive Hydrogel Promotes Spinal Cord Repair by Regulating Mitochondrial Function

“…Besides, the alive UCMSC cells in the bFGF-ECM-HP hydrogel were more than that in the ECM-HP hydrogel after being cultured for 48 h. The outcomes of CCK-8 assay revealed that bFGF promoted the expansion of UCMSC and improved the survival rate of UCMSC in vitro (Figure B). Numerous studies have shown that bFGF could enhance neuronal cell fate determination and differentiation. , UCMSC has the capability to naturally release multicytokines and differentiate into nerve cells. , To gain further insights into the interactions between bFGF and UCMSC, the content of bFGF was measured by ELISA. In Figure C, the results of ELISA showed that UCMSC secreted a large number of bFGF significantly by bFGF stimulation during culture.…”

“…Numerous studies have shown that bFGF could enhance neuronal cell fate determination and differentiation. 24,25 UCMSC has the capability to naturally release multicytokines and differentiate into nerve cells. 26,27 To gain further insights into the interactions between bFGF and UCMSC, the content of bFGF was measured by ELISA.…”

Accelerated Healing of Infected Diabetic Wounds by a Dual-Layered Adhesive Film Cored with Microsphere-Loaded Hydrogel Composite Dressing

“…60 Due to its protective effect on endothelial impairment and chronic inflammation induced by hyperglycemia via the S-nitrosylation pathway, the bFGF has provided new insights into the management of nonhealing diabetic ulcers and associated lesions. 61 Considering the short half-life of bFGF and enzymatic degradation, various delivery systems have been tested for controlling the release of such growth factors. 20,21 In Figure 8.…”

The NO Answer for Autism Spectrum Disorder

“…23 479) using the manufacturer's instructions. [ 97 ] A fresh brain was used for this assay. The homogenate was prepared in PBS and filtered with a 10WCO centrifuge tube.…”