Hui Ding, Anna Zhao, Xia Chen, Yanli Niu, Yuanyuan Wang, Xiao Chen, Hong Yang*
Department of Obstetrics, Xuyi County People’s Hospital, Xuyu, Huai’an, Jiangsu 211700, China.
- Corresponding Author:Hong Yang; E-mail: yanghong_edu@outlook.com
Abstract
Background
Gestational diabetes mellitus (GDM) is characterized by systemic immune dysregulation and chronic inflammation that contribute to insulin resistance and β-cell dysfunction. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in several inflammatory disorders; however, its role in GDM-related immune and metabolic disturbances remains unclear.
Methods
A mouse model of GDM and insulin-resistant trophoblast cells were used to evaluate MALAT1 expression and its effects on inflammatory cytokines and β-cell apoptosis. Gene expression was analyzed by qRT-PCR and Western blotting, while histological and biochemical assays assessed pancreatic morphology, serum glucose, and inflammatory cytokine levels. Functional and rescue experiments were performed to explore the molecular interaction between MALAT1, miR-576-5p, and HNRNPU.
Results
MALAT1 expression was markedly elevated in GDM mice and insulin-resistant trophoblasts, correlating with increased levels of TNF-α, IL-1β, and IL-6, as well as enhanced β-cell apoptosis. Silencing MALAT1 alleviated hyperglycemia, preserved pancreatic islet structure, and reduced inflammatory mediator secretion. Mechanistically, MALAT1 acted as a competing endogenous RNA by sponging miR-576-5p to upregulate HNRNPU, thereby promoting NF-κB activation. HNRNPU overexpression reversed the anti-inflammatory and anti-apoptotic effects of MALAT1 knockdown.
Conclusion
MALAT1 promotes immune-metabolic dysfunction in GDM through the miR-576-5p/HNRNPU/NF-κB axis. Targeting this pathway may offer a novel therapeutic strategy for reducing inflammation-associated complications in GDM.
Keywords: Gestational diabetes mellitus, MALAT1, HNRNPU, miR-576-5p, immune dysregulation, pro-inflammatory cytokines