Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, China.
Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Chengdu, Sichuan, China.
Anim Biotechnol. 2023 Apr;34(2):365-374. doi: 10.1080/10495398.2021.1968885. Epub 2021 Aug 30.
The rapid healing of impaired intestinal surface plays a role in maintaining intestinal homeostasis. This study investigated the effect of calcium-sensing receptor (CaSR) on the migration and proliferation of intestinal porcine epithelial cells (IPEC-J2). Results showed that cell migration area and width were increased by R568 (CaSR activator) and decreased by NPS2143 (CaSR inhibitor). The protein level of GTP-rac1 and the phosphorylation of phospholipase C gamma 1 (PLCγ1) were increased by 2 µM R568. Furthermore, R568 + 120 µM NSC23766 (Rac1 inhibitor) and R568 + 1 µM U73122 (PLCγ1 inhibitor) decreased the protein level of GTP-rac1 and the phosphorylated PLCγ1, respectively, and both inhibited cell migration compared with R568. In addition, spermine increased the protein expression levels of CaSR and the levels of GTP-rac1 and the phosphorylated PLCγ1 and thereby promoted the migration of IPEC-J2 cells. Moreover, R568 improved the proliferation of the IPEC-J2 cells. Spermine increased cell proliferation, but NPS2143 incubated with spermine decreased cell proliferation compared with the spermine group. This study suggests that CaSR activation increased cell migration by activating Rac1 and PLCγ1 signaling and improved cell proliferation, and both effects were regulated by spermine by activating CaSR.
快速修复受损的肠道表面在维持肠道内稳态中发挥作用。本研究探讨了钙敏感受体（CaSR）对猪肠上皮细胞（IPEC-J2）迁移和增殖的影响。结果表明，R568（CaSR 激活剂）增加了细胞迁移面积和宽度，而 NPS2143（CaSR 抑制剂）则降低了细胞迁移面积和宽度。2 μM R568 增加了 GTP-rac1 蛋白水平和磷脂酶 C 伽马 1（PLCγ1）的磷酸化。此外，R568+120 μM NSC23766（Rac1 抑制剂）和 R568+1 μM U73122（PLCγ1 抑制剂）分别降低了 GTP-rac1 和磷酸化 PLCγ1 的蛋白水平，与 R568 相比，这两种抑制剂均抑制了细胞迁移。此外，亚精胺增加了 CaSR 的蛋白表达水平以及 GTP-rac1 和磷酸化 PLCγ1 的水平，从而促进了 IPEC-J2 细胞的迁移。此外，R568 改善了 IPEC-J2 细胞的增殖。亚精胺增加了细胞增殖，但与亚精胺组相比，与 NPS2143 孵育的亚精胺降低了细胞增殖。本研究表明，CaSR 激活通过激活 Rac1 和 PLCγ1 信号通路增加细胞迁移，并改善细胞增殖，这两种作用均受 CaSR 激活的亚精胺调节。
