Igfbp1-flox Mouse

Igfbp1, insulin-like growth factor binding protein 1, is a protein-coding gene. It binds to insulin-like growth factors (IGFs), modulating their bioavailability and activity, thus playing a role in multiple biological processes such as cell growth, metabolism, and differentiation. The IGF signaling pathway is one of the main associated pathways [6].

In pregnancy-related studies, placental Igfbp1 expression positively associates with insulin sensitivity at around 26 weeks of gestation. Low circulating Igfbp1 levels in early pregnancy can predict subsequent gestational diabetes mellitus (GDM) diagnosis, implicating its role in pregnancy glycemic physiology [1].

In preeclampsia, Igfbp1 expression in the placenta is increased. Overexpression of Igfbp1 in HTR-8/SVneo trophoblast cells inhibits their proliferation, invasion, migration, and apoptosis, and is related to MMP-26 expression, suggesting its role in preeclampsia pathophysiology [2]. Also, in Chinese Han women, the Igfbp1 SNP rs1065780A > G is associated with a decreased risk of preeclampsia, with the G genotype increasing Igfbp1 protein levels and improving pregnancy outcomes [4].

In cystitis, Igfbp1 suppresses its occurrence and development by stabilizing Umod expression through m6A modification, inhibiting the NF-κB and ERK signaling pathways [3].

In diabetes-related research, in prediabetic patients, lower IGF1 and higher Igfbp1 predict the incidence of type 2 diabetes mellitus (T2DM), indicating an impairment of beta-cell function [5]. In zebrafish, Igfbp1 promotes β-cell regeneration by potentiating α-to β-cell transdifferentiation, and in human islets, treatment with recombinant Igfbp1 in vitro increases the number of cells co-expressing insulin and glucagon, and high Igfbp1 levels reduce the risk of developing type-2 diabetes [6].

In gastric cancer, high Igfbp1 expression is associated with haematogenous metastasis and poor survival, and in stomach adenocarcinoma, low Igfbp1 mRNA expression is related to a shorter overall survival time, and Igfbp1 may inhibit immune cell infiltration in tumors [7,8]. In colorectal cancer, histone MARylation promotes Igfbp1 methylation, regulating lipid metabolism [9].

In conclusion, Igfbp1 is a gene with diverse functions, playing crucial roles in pregnancy-related diseases like GDM and preeclampsia, as well as in diseases such as cystitis, diabetes, and various cancers. Studies on Igfbp1 contribute to understanding the underlying mechanisms of these diseases, potentially providing new directions for diagnosis and treatment.