维生素A通过IGF1和Wnt10b信号通路在热应激下调节真皮乳头细胞的增殖和凋亡。

Vitamin A regulates dermal papilla cell proliferation and apoptosis under heat stress via IGF1 and Wnt10b signaling.

作者信息

Yue Zhengkai, Liu Mengqi, Zhang Bin, Li Fan, Li Chenyang, Chen Xiaoyang, Li Fuchang, Liu Lei

机构信息

Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China.

出版信息

Ecotoxicol Environ Saf. 2023 Aug 8;262:115328. doi: 10.1016/j.ecoenv.2023.115328.

DOI:10.1016/j.ecoenv.2023.115328

PMID:37562175

Abstract

Heat stress (HS) negatively affects the development of hair follicles. The present study investigated the effect of vitamin A (VA) on the development of rabbit dermal papilla cells (DPCs) under HS and the underlying regulatory mechanisms. Addition of 0.4 mg/L VA to the culture medium significantly enhanced cell proliferation (P < 0.001) and inhibited the apoptosis of DPCs (P < 0.01). VA decreased the proportion of DPCs in G0/G1 stage of the cell cycle under HS along with the expression of caspase 3, heat shock protein 70 (HSP70), and microRNA 195 (miR-195) (P < 0.05). VA also activated the insulin-like growth factor 1 (IGF1) and Wnt10b/β-catenin signaling pathways. The results of the dual luciferase reporter assay showed that IGF1 expression was modulated by miR-195-5p. Over-expression of miR-195-5p in DPCs with HS+VA treatment significantly reduced cell viability and IGF1 signaling (P < 0.01) and increased apoptosis (P < 0.01) compared with the HS+VA group. The positive effects of VA on proliferation and apoptosis of DPCs under HS were significantly attenu-ated by blocking Wnt10b and β-catenin signaling with IWP-2 and XAV-939, respectively. These results demonstrate that VA can promote hair follicle development following HS via modulation of miR-195/IGF1 and Wnt10b/β-catenin signaling pathways.

摘要

热应激（HS）对毛囊发育产生负面影响。本研究调查了维生素A（VA）对热应激条件下兔真皮乳头细胞（DPCs）发育的影响及其潜在调控机制。向培养基中添加0.4mg/L VA可显著增强细胞增殖（P<0.001）并抑制DPCs的凋亡（P<0.01）。VA降低了热应激条件下处于细胞周期G0/G1期的DPCs比例，同时降低了半胱天冬酶3、热休克蛋白70（HSP70）和微小RNA 195（miR-195）的表达（P<0.05）。VA还激活了胰岛素样生长因子1（IGF1）和Wnt10b/β-连环蛋白信号通路。双荧光素酶报告基因检测结果表明，IGF1表达受miR-195-5p调控。与热应激+VA组相比，热应激+VA处理的DPCs中miR-195-5p过表达显著降低了细胞活力和IGF1信号（P<0.01），并增加了细胞凋亡（P<0.01）。分别用IWP-2和XAV-939阻断Wnt10b和β-连环蛋白信号通路后，VA对热应激条件下DPCs增殖和凋亡的积极作用显著减弱。这些结果表明，VA可通过调节miR-195/IGF1和Wnt10b/β-连环蛋白信号通路促进热应激后的毛囊发育。