Mechanisms of LncRNA FTX in Regulating Islet Function of Pregnant Mice Born With Low-Protein Diet-Induced Intrauterine Growth Retardation.

Abstract

Glucose metabolism during pregnancy in adult females born with intrauterine growth restriction (IUGR) remains inadequately understood. This study aims to investigate how LncRNA FTX regulates islet function during pregnancy in F1 female mice born with IUGR (F1 IUGR pregnant mice). A pregnant mouse model was established using F1 female mice born with IUGR (F1 IUGR pregnant mouse model). Intraperitoneal glucose tolerance test (IPGTT), immunohistochemistry (IHC) staining, quantitative real-time PCR (qPCR) were performed in both F1 IUGR and normal mice during pregnancy and non-pregnancy periods. RNA-sequencing was conducted on islets from F1 IUGR and normal pregnant mice. Insulin-related gene expression analysis, cell proliferation, and apoptosis assessment were performed in TC6 cells following FTX knockdown or overexpression. A luciferase reporter assay was conducted to validate the molecular interactions. F1 IUGR pregnant mice exhibited a smaller increase in insulin-staining area and lower upregulation of insulin-related gene expression levels compared to normal pregnant mice. There were 1,007 differentially expressed lncRNAs between F1 IUGR and normal pregnant islets; among these, FTX was down-regulated during pregnancy, although its downregulation in F1 IUGR pregnant mice was less pronounced than in normal pregnant mice. FTX was closely related to cell proliferation activity, apoptosis, insulin-related transcription factor expression. The pten/PI3K/AKT pathway was also regulated by FTX. Luciferase reporter assay confirmed FTX acted as a competing endogenous RNA (CeRNA) to target pten by sponging miR-22-3p. LncRNA FTX regulates islet function during pregnancy in F1 mice born with IUGR via the miR-22-3p/pten axis.