Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

COLEC12 expression participates in trophoblast insulin resistance, and reverses celecoxib-mediated inhibition of COX2-PGE2 axis in gestational diabetes

Beibei Jin¹, Mi Hu², Jie Chen³, Lin Yu⁴

¹Department Pediatric Clinic, Wuhan Third Hospital, Wuhan City, Hubei Province 430074, China; ²Department of Pediatrics, Wuhan Third Hospital, Wuhan City, Hubei Province 430074, China; ³Department of Nephrology, Wuhan Third Hospital, Wuhan City, Hubei Province 430074, China; ⁴Department of Gynecology and Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province 225003, China.

For correspondence:- Lin Yu Email: Yulin_668@163.com Tel:+8651482981199

Accepted: 6 May 2023 Published: 30 May 2023

Citation: Jin B, Hu M, Chen J, Yu L. COLEC12 expression participates in trophoblast insulin resistance, and reverses celecoxib-mediated inhibition of COX2-PGE2 axis in gestational diabetes. Trop J Pharm Res 2023; 22(5):959-965 doi: 10.4314/tjpr.v22i5.4

© 2023 The authors.
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Abstract

Purpose: To evaluate the contribution of collectin subfamily member 12 (COLEC12) in insulin resistance associated with gestational diabetes mellitus (GDM).

Methods: Insulin resistance was induced in human placental trophoblast (HTR-8/SVneo) cells in vitro by incubating them with 1 μM insulin for 48 h. expression of COLEC12 was assessed using western blot and quantitative real time-polymerase chain reaction (qRT-PCR). Distribution of glucose transporters GLUT1 and GLUT4 was visualized using immunofluorescent staining. Furthermore, the level of reactive oxygen species (ROS) was evaluated by flow cytometry.

Results: Insulin-resistant HTR-8/SVneo (IR-HTR-8/SVneo) cells showed significantly elevated COLEC12 expression (p < 0.001). Knocking down of COLEC12 in these cells led to a significant reduction in GLUT1 expression, and increase in both glucose consumption and GLUT4 expression (p < 0.001). Furthermore, COLEC12 knockdown levels of ROS increased SOD expression in IR-HTR-8/SVneo, while knockdown of COLEC12 reduced p-insulin receptor substrate (IRS) (Ser307) protein expression, but increased p-IRS-1 (Tyr896), p-insulin receptor β (IRβ) (Tyr1361), and p-AKT levels. COLEC12 knockdown also decreased cyclooxygenase-2 (COX-2) expression, resulting in lower prostaglandin E2 (PGE2) levels in IR-HTR-8/SVneo. COLEC12 over-expression attenuated celecoxib-induced increase in glucose consumption, resulting in decreased COX2 and PGE2 levels.

Conclusion: COLEC12 in IR-HTR-8/SVneo cells has antioxidant effects that protect against insulin resistance. This protective effect is achieved through the down-regulation of COX-2/PGE2. These findings provide a potential strategy for the treatment of GDM

Keywords: COLEC12, Insulin resistance, COX-2, PGE2, Oxidative stress, Gestational diabetes mellitus