The DR1-CSE/[H.sub.2]S system inhibits renal fibrosis by downregulating the ERK1/2 signaling pathway in diabetic mice

Glomerular mesangial cell (MC) proliferation and extracellular matrix deposition are the main pathological changes in diabetic nephropathy. Hydrogen sulfide (H2S) inhibits the proliferation of MCs. Dopamine 1 receptors (DR1) are expressed in MCs and serve important physiological roles. However, it i...

Full description

Saved in:
Bibliographic Details
Published inInternational journal of molecular medicine Vol. 49; no. 1; p. 1
Main Authors Li, Hongzhu, Sun, Fengqi, Bai, Shuzhi, Chang, Guiquan, Wu, Ren, Wei, Yaxin, Wen, Xin, Xi, Yuxin, Hao, Jinghui, Zaid, Altaany
Format Journal Article
LanguageEnglish
Published Spandidos Publications 01.01.2022
Subjects
Diabetic nephropathies
Dopamine
Hydrogen sulfide
Muscle proteins
China
Online AccessGet full text

Cover

More Information
Summary:Glomerular mesangial cell (MC) proliferation and extracellular matrix deposition are the main pathological changes in diabetic nephropathy. Hydrogen sulfide (H2S) inhibits the proliferation of MCs. Dopamine 1 receptors (DR1) are expressed in MCs and serve important physiological roles. However, it is unclear whether DR1 activation inhibits MC proliferation by increasing endogenous [H.sub.2]S. The present study found that the production of [H.sub.2]S and the expression of DR1 and cystathionine-[gamma]-lyase (CSE) were decreased in the renal tissues of diabetic mice and high glucose (HG)-induced MCs. SKF38393 (a DR1 agonist) increased the production of [H.sub.2]S and the expression of DR1 and CSE and NaHS (an exogenous [H.sub.2]S donor) only increased [H.sub.2]S production and CSE expression but not DR1 expression. HG increased the thickness of the glomerular basement membrane, cell viability and proliferation, the expression of cyclin D1, PCNA, collagen 1 and [alpha]-smooth muscle actin and the activity of phosphorylated ERK1/2 and decreased the expression of P21 and MMP9. SKF38393 and NaHS reversed the effects of HG. PPG (a CSE inhibitor) abolished the beneficial effects of SKF38393. The beneficial effects of SKF38393 were similar to those of PD98059 (an ERK1/2 inhibitor). Taken together, the findings suggested that the DR1-CSE/[H.sub.2]S pathway activation attenuated diabetic MC proliferation and extracellular matrix deposition by downregulating the ERK1/2 signaling pathway. Key words: dopamine 1 receptors, hydrogen sulfide, glomerular mesangial cells, proliferation, diabetic nephropathy
ISSN:1107-3756
DOI:10.3892/ijmm.2021.5062