Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Traditional Chinese Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Connect Tissue Res. 2022 Sep;63(5):498-513. doi: 10.1080/03008207.2021.2025225. Epub 2022 Feb 7.
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.
V 型胶原蛋白（胶原 V）是胰腺细胞外基质（ECM）的重要组成部分之一。我们之前的研究报道，在培养皿上预先涂覆胶原 V 可增强 INS-1 大鼠胰岛β细胞的胰岛素分泌。在本研究中，我们探究了其潜在的机制。
在胶原 V 包被的培养皿中培养的 INS-1 细胞中，胰岛素的生物合成和分泌均增加，同时 Yes 相关蛋白（YAP）的核易位减少，YAP 是 Hippo 信号通路的转录共激活因子，在胰腺的发育和功能中起重要作用。通过verteporfin 抑制 YAP 的激活可进一步上调胰岛素的生物合成和分泌。通过 siRNA 转染沉默 Hippo 通路的核心成分——大肿瘤抑制因子（LATS），其通过磷酸化抑制 YAP 的活性，可同时抑制胰岛素的生物合成和分泌。在本研究中，IGF-1 受体（IGF-1R）的蛋白水平降低，IGF-1R 是 YAP 的上游分子，在胶原 V 包被的培养皿中培养的 INS-1 细胞中。IGF-1R 的 siRNA 转染沉默进一步增强了胰岛素的生物合成和分泌。IGF-1 处理可降低胶原 V 诱导的胰岛素生物合成和分泌的上调，伴随核 YAP 的增加。
抑制 IGF-1R/YAP 信号通路参与了胶原 V 诱导的 INS-1 细胞胰岛素的生物合成和分泌。
