Endoplasmic reticulum stress induces growth retardation by inhibiting growth hormone IGF-I axis

Wanjun Xia*, Yajun Wang, Yong Zhang, Xin Ge, Pengwei Lv, Jingliang Cheng, Juncheng Wei

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Insulin-like growth factor 1 (IGF[sbnd]I) is one of several growth factors which is induced by growth hormone (GH), which activates the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathway, and plays crucial roles in normal human growth, metabolism, and systemic energy homeostasis. However, little is known about the negative regulation of IGF-I production under different physiological or pathological conditions. Herein, we explore whether activation of endoplasmic reticulum (ER) stress regulates IGF-I production and normal body growth. Materials and methods: C57BL/6 J mice were challenged with tunicamycin (Tm) to induce ER stress activation. 24 h after stimulation, hepatic mRNA expression was analyzed by RNA-Seq and validated by qPCR. Enzyme-linked immunosorbent assay (ELISA) was performed 24 h after Tm stimulation. Body growth was determined 16 days after Tm stimulation. Animals were then sacrificed and liver tissues were collected for further analysis. Results: Mice challenged with Tm displayed a retardation of growth. Molecularly, we found that ER stress inhibited phosphorylation of STAT5. IGF-I transcription and circulating IGF-I were also dramatically decreased under ER stress activation. Moreover, our results demonstrate that IGF-I administration ameliorates Tm-induced growth retardation. Conclusions: ER stress induces growth retardation. ER stress inhibits hepatic GH-JAK2 signaling activation and its downstream target gene expression. These results warrant further research to explore the crosstalk between ER stress and growth hormone signaling in improving body growth.

Original languageEnglish (US)
Article number101341
JournalGrowth Hormone and IGF Research
Volume55
DOIs
StatePublished - Dec 2020

Keywords

  • Body growth
  • ER stress
  • IGF-I

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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