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  • Title: Periostin Acts as a Bridge between Gestational Diabetes Mellitus (GDM) and Chronic Inflammation to Modulate Insulin Resistance by Modulating PPARα/NF-κB/TNF-α Signaling Pathway.
    Author: Ji Q, Li X, Wang Y, Liu H, Chen K, Quan H, Zhang H, Ran J.
    Journal: Endocr Metab Immune Disord Drug Targets; 2023; 23(13):1649-1659. PubMed ID: 37106515.
    Abstract:
    INTRODUCTION: Gestational diabetes mellitus (GDM) is considered an imbalance of glucose metabolism and insulin resistance during pregnancy. AIMS/OBJECTIVE: To evaluate the levels of periostin (POSTN) in patients with GDM and investigate the association between POSTN and GDM. MATERIALS AND METHODS: A total of 30 pregnant women (NC group) and 30 pregnant women with GDM (GDM group) were involved. The GDM mouse model was established by intraperitoneally injecting streptozotocin. The oral glucose tolerance test (OGTT), insulin, and insulin resistance indices were tested. An immunohistochemical and Western blot assay was conducted to determine the expression of POSTN, PPARα, TNF-α, and NF-κB. HE staining was performed to evaluate inflammation in the placental tissues of women with GDM and GDM mice. POSTN-siRNA was transfected into glucose-pretreated HTR8 cells, and pAdEasy-m-POSTN shRNA was infected in GDM mice. The RT-PCR assay determined the gene transcription of POSTN, TNF-α, NF-κB, and PPARα. RESULTS: Pregnantwomen in theGDMgroup demonstrated significantly higherOGTT (p < 0.05), insulin levels (p < 0.05) and insulin resistance (p < 0.05) compared to those of the NC group. The serum levels of POSTN in pregnantwomen of theGDMgroup were significantly higher than that of theNC group (p < 0.05). The obvious inflammation was activated in pregnant women in the GDMgroup. POSTN-siRNAsignificantly enhanced the cell viability of glucose-treated HTR8 cells compared to that without glucose treatment (p < 0.05). POSTNsiRNA (pAdEasy-m-POSTN shRNA) markedly reduced the glucose level of glucose-treated HTR8 cells (GDM mice) compared to that without treatment (p < 0.05). POSTN-siRNA (pAdEasy-m-POSTN shRNA) promoted PPARα gene transcription (p < 0.05) and inhibited NF-κB/TNF-α gene transcription (p < 0.05) in glucose-treated HTR8 cells (GDMmice) compared to thosewithout treatment. POSTN-siRNAmodulated NF- κB/TNF-α pathway mediated inflammation by regulating PPARα in HTR8 cells and GDMmice. PPARα participated in POSTN-associated inflammation. pAdEasy-m-POSTN shRNA inhibited T-CHO/TG levels in GDM mice compared to those without treatment (p < 0.05). All the effects of POSTN-siRNA (pAdEasy-m- POSTN shRNA) were obviously blocked by PPARα inhibitor treatment. CONCLUSION: POSTN levels were significantly higher in pregnant women with GDM and were associated with chronic inflammation and PPARα expression. POSTN may act as a bridge between GDM and chronic inflammation to modulate insulin resistance by modulating PPARα/NF-κB/TNF-α signaling pathway.
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