1. IGF-1R/YAP signaling pathway is involved in collagen V-induced insulin biosynthesis and secretion in rat islet INS-1 cells.
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Zhu, Yingying, Chen, Shuaigao, Liu, Weiwei, Xu, Fanxing, Lu, Jingyu, Hayashi, Toshihiko, Mizuno, Kazunori, Hattori, Shunji, Fujisaki, Hitomi, and Ikejima, Takashi
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HIPPO signaling pathway ,BIOSYNTHESIS ,INSULIN-like growth factor receptors ,SOMATOMEDIN C ,ISLANDS of Langerhans ,INSULIN ,INSULIN receptors ,WNT signal transduction - Abstract
Type V collagen (collagen V) is one of the important components of extracellular matrix (ECM) in pancreas. We previously reported that pre-coating collagen V on the culture dishes enhanced insulin production in INS-1 rat pancreatic β cells. In this study, we investigate the underlying mechanism. Insulin biosynthesis and secretion are both increased in INS-1 cells cultured on collagen V-coated dishes, accompanied by the reduced nuclear translocation of Yes-associated protein (YAP), a transcriptional co-activator. YAP, the downstream effector of Hippo signaling pathway, plays an important role in the development and function of pancreas. Inhibition of YAP activation by verteporfin further up-regulates insulin biosynthesis and secretion. Silencing large tumor suppressor (LATS), a core component of Hippo pathway which inhibits activity of YAP by phosphorylation, by siRNA transfection inhibits both insulin biosynthesis and secretion. In the present study, the protein level of insulin-like growth factor 1 receptor (IGF-1 R), detected as the upstream molecule of YAP, is reduced in the INS-1 cells cultured on the dishes coated with collagen V. The silencing of IGF-1 R by siRNA transfection further enhances insulin biosynthesis and secretion. IGF-1 treatment reduces collagen V–induced up-regulation of insulin biosynthesis and secretion, accompanying the increased nuclear YAP. Inhibition of IGF-1 R/YAP signal pathway is involved in collagen V–induced insulin biosynthesis and secretion in INS-1 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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