Roles of retinoic acid-related orphan receptor α in high glucose-induced cardiac fibroblasts proliferation DOI Creative Commons

Wenqing San,

Qianyou Zhou,

Danning Shen

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Diabetic cardiomyopathy, characterized by myocardial fibrosis, is a common complication of diabetes. Retinoic acid-related orphan receptor α (RORα) participates in various pathological and physiological cardiovascular processes. The current research aims to elucidate the roles mechanisms RORα high glucose induced cardiac fibroblasts proliferation. Primary neonatal were isolated from Sprague-Dawley rats, pre-administrated with antagonist SR3335 (20 µM) or agonist SR1078 (10 followed stimulation normal (5.5 mM) (33.3 respectively. Lactate Dehydrogenase (LDH) release into culture medium, cellular adenosine-triphosphate (ATP), cell number detected. Expressions Collagen I, III, proliferating nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), receptor-interacting protein kinase 1 (RIPK1) 3 (RIPK3) evaluated. extent oxidative stress was also assessed. Our study found that elevated LDH release, reduced ATP production, increased cells numbers, expression PCNA, α-SMA, RIPK1 RIPK3, decreased mitochondrial membrane potential, strengthened intensity dihydroethidium (DHE) MitoSOX fluorescence. Above effects all further exacerbated but significantly reversed SR1078. In conclusion, promoted injury proliferation, enhanced collagen synthesis, facilitated necroptosis stimulation, whereas showed opposing effects. proposed as novel target against glucose-induced which beneficial clarify ideal therapeutic implication for diabetic cardiomyopathy.

Language: Английский

Roles of retinoic acid-related orphan receptor α in high glucose-induced cardiac fibroblasts proliferation DOI Creative Commons

Wenqing San,

Qianyou Zhou,

Danning Shen

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Diabetic cardiomyopathy, characterized by myocardial fibrosis, is a common complication of diabetes. Retinoic acid-related orphan receptor α (RORα) participates in various pathological and physiological cardiovascular processes. The current research aims to elucidate the roles mechanisms RORα high glucose induced cardiac fibroblasts proliferation. Primary neonatal were isolated from Sprague-Dawley rats, pre-administrated with antagonist SR3335 (20 µM) or agonist SR1078 (10 followed stimulation normal (5.5 mM) (33.3 respectively. Lactate Dehydrogenase (LDH) release into culture medium, cellular adenosine-triphosphate (ATP), cell number detected. Expressions Collagen I, III, proliferating nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), receptor-interacting protein kinase 1 (RIPK1) 3 (RIPK3) evaluated. extent oxidative stress was also assessed. Our study found that elevated LDH release, reduced ATP production, increased cells numbers, expression PCNA, α-SMA, RIPK1 RIPK3, decreased mitochondrial membrane potential, strengthened intensity dihydroethidium (DHE) MitoSOX fluorescence. Above effects all further exacerbated but significantly reversed SR1078. In conclusion, promoted injury proliferation, enhanced collagen synthesis, facilitated necroptosis stimulation, whereas showed opposing effects. proposed as novel target against glucose-induced which beneficial clarify ideal therapeutic implication for diabetic cardiomyopathy.

Language: Английский

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