Wanjun Xia1, Yajun Wang2, Yong Zhang3, Xin Ge4, Pengwei Lv4, Jingliang Cheng5, Juncheng Wei6. 1. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: 191923009@qq.com. 2. Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Heilongjiang 150001, China. 3. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. 4. Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. 5. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: cjl2857@126.com. 6. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: juncheng.wei@northwestern.edu.
Abstract
OBJECTIVE: Insulin-like growth factor 1 (IGFI) 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.
OBJECTIVE:Insulin-like growth factor 1 (IGFI) 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.
Authors: Laura Di Patria; Giosuè Annibalini; Amelia Morrone; Lorenzo Ferri; Roberta Saltarelli; Luca Galluzzi; Aurora Diotallevi; Matteo Bocconcelli; Maria Alice Donati; Rita Barone; Renzo Guerrini; Jaak Jaeken; Vilberto Stocchi; Elena Barbieri Journal: Cell Mol Life Sci Date: 2022-02-24 Impact factor: 9.207