Endoplasmic reticulum stress induces growth retardation by inhibiting growth hormone IGF-I axis.
Growth Horm IGF Res
; 55: 101341, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-32890915
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Hormônio do Crescimento
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Estresse do Retículo Endoplasmático
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Transtornos do Crescimento
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article