IGF1R Enhances Calcium Oxalate Monohydrate-Induced Epithelial-Mesenchymal Transition by Reprogramming Metabolism Via the JAK2/STAT3 Signaling

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2025 Jan 2

PMID 39744436

Authors

Jiashan Pan

Yi Zhang

Rui Yao

Mo Yang

Xike Mao

Zhenyu Song

Yuexian Xu

Yang Chen

Bingbing Hou

Xiaoying Liu

Wei Wang

Zongyao Hao

Affiliations

Soon will be listed here.

Abstract

Kidney stone disease is a major risk factor for impaired renal function, leading to renal fibrosis and end-stage renal disease. High global prevalence and recurrence rate pose a significant threat to human health and healthcare resources. Investigating the mechanisms of kidney stone-induced injury is crucial. We examined the relationship between insulin-like growth factor 1 receptor (IGF1R) and epithelial-mesenchymal transition (EMT) at three levels: in patients with kidney stones, in mice induced with glyoxalate crystals, and in HK2 cells stimulated with calcium oxalate monohydrate (COM). RNA sequencing (RNA-seq) and untargeted metabolomics were used to investigate IGF1R's biological mechanisms, followed by alidation in mice. IGF1R was elevated in the kidney stone model, which was significantly associated with EMT progression. RNA-seq analysis indicated that IGF1R enhances EMT through the JAK2/STAT3 pathway. Further experiments at mRNA and protein levels confirmed the activation of this pathway regulated by IGF1R, promoting EMT. Additionally, untargeted metabolomics revealed that IGF1R drives the activation of lactate dehydrogenase A (LDHA) in glycolysis, further facilitating EMT. experiments confirmed that IGF1R increases LDHA activity through the activation of the JAK2/STAT3 pathway, thereby enhancing the EMT. IGF1R promotes EMT in COM-induced kidney injury by activating LDHA via the JAK2/STAT3 signaling.

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