IGF-1R/YAP signaling pathway is involved in collagen V-induced insulin biosynthesis and secretion in rat islet INS-1 cells

  • Connect Tissue Res. 2022 Sep;63(5):498-513. doi: 10.1080/03008207.2021.2025225.
Yingying Zhu  1  2 ,  Shuaigao Chen  1 ,  Weiwei Liu  1 ,  Fanxing Xu  1 ,  Jingyu Lu  1 ,  Toshihiko Hayashi  1  3  4 ,  Kazunori Mizuno  4 ,  Shunji Hattori  4 ,  Hitomi Fujisaki  4 ,  Takashi Ikejima  1  5
Affiliations
  • 1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • 2. Traditional Chinese Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
  • 3. Department of Chemistry and Life Science, School of Advanced Engineering Kogakuin University, Tokyo, Japan.
  • 4. Nippi Research Institute of Biomatrix, Toride, Ibaraki, Japan.
  • 5. Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
PMID: 35129018 DOI: 10.1080/03008207.2021.2025225
Abstract

Purpose: 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.

Results: 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.

Conclusion: Inhibition of IGF-1 R/YAP signal pathway is involved in Collagen V-induced Insulin biosynthesis and secretion in INS-1 cells.

Keywords
IGF-1R; Type 1 diabetes mellitus; YAP; collagen V.
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