Reg3g,也称为Regenerating islet-derived protein 3 gamma,是Reg家族成员之一,是一类在胰腺β细胞再生和抗炎反应中发挥重要作用的蛋白质。Reg3g在多种生物学过程中发挥作用,包括细胞分化、发育、代谢和疾病发生。
Reg3g在骨骼肌和神经再生中发挥重要作用。研究发现,在肌肉和神经损伤后,Reg3g基因在比目鱼肌和伸趾长肌及其对应的神经中转录激活,表明Reg3g基因在受损轴突和肌肉之间的通讯中发挥重要作用,可能在骨骼肌和周围神经再生中发挥显著作用[1]。
Reg3g在脑转移中发挥重要作用。研究发现,lnc-REG3G-3-1/miR-215-3p轴通过调节Leptin和SLC2A5的信号通路,参与肺腺癌脑转移的过程[2]。
Reg3g在肠道炎症中发挥重要作用。研究发现,细菌来源的长链脂肪酸C18-3OH具有抗炎作用,可以通过激活过氧化物酶体增殖物激活受体γ来改善结肠炎。此外,Reg3g在肠上皮细胞中被IL33-STAT3信号通路上调,并抑制PEDV的复制[3,6]。
Reg3g在非酒精性脂肪性肝病(NASH)中发挥重要作用。研究发现,Reg3g在NASH的进展中表达下调,而中药枳实可以显著上调Reg3g的表达,改善肠道屏障功能,降低内毒素转移,从而改善NASH[4]。
Reg3g在β细胞功能障碍和1型糖尿病中发挥重要作用。研究发现,Reg3g可以改善他克莫司诱导的β细胞功能障碍,通过恢复线粒体功能来逆转他克莫司诱导的糖尿病。此外,Reg3g过表达可以促进β细胞再生,并通过增加调节性T细胞分化来诱导免疫耐受,从而预防1型糖尿病[5,7]。
Reg3g在胰腺癌中发挥重要作用。研究发现,Reg3g在慢性胰腺炎和胰腺癌中异常表达,通过多种机制促进胰腺癌的发生和发展,包括增强胰腺肿瘤标志物的转录、抑制抗肿瘤免疫和激活STAT3/p65信号传导途径[8,9]。
综上所述,Reg3g是一种重要的蛋白质,在多种生物学过程中发挥作用,包括细胞分化、发育、代谢和疾病发生。Reg3g在骨骼肌和神经再生、脑转移、肠道炎症、NASH、β细胞功能障碍和1型糖尿病、胰腺癌中发挥重要作用。Reg3g的研究有助于深入理解其生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Klasan, Gordana Starcevic, Ivanac, Danijel, Erzen, Dubravka Jurisic, Girotto, Dean, Jerkovic, Romana. 2013. Reg3G gene expression in regenerating skeletal muscle and corresponding nerve. In Muscle & nerve, 49, 61-8. doi:10.1002/mus.23877. https://pubmed.ncbi.nlm.nih.gov/23588857/
2. Jiang, Chunyang, Zhao, Hui, Yang, Bingjun, Li, Xin, Hu, Xiaoli. 2020. lnc-REG3G-3-1/miR-215-3p Promotes Brain Metastasis of Lung Adenocarcinoma by Regulating Leptin and SLC2A5. In Frontiers in oncology, 10, 1344. doi:10.3389/fonc.2020.01344. https://pubmed.ncbi.nlm.nih.gov/32903414/
3. Pujo, Julien, Petitfils, Camille, Le Faouder, Pauline, Cani, Patrice D, Cenac, Nicolas. 2020. Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis. In Gut, 70, 1088-1097. doi:10.1136/gutjnl-2020-321173. https://pubmed.ncbi.nlm.nih.gov/32978245/
4. Yan, Junbin, Nie, Yunmeng, Chen, Xinli, Ding, Menglu, Zhang, Shuo. 2024. Mechanistic study of fructus aurantii (Quzhou origin) in regulating ileal reg3g in the treatment for NASH. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 133, 155924. doi:10.1016/j.phymed.2024.155924. https://pubmed.ncbi.nlm.nih.gov/39098169/
5. Li, Senlin, Zhou, Hong, Xie, Mengyuan, Peng, Wen, Xiang, Ming. 2022. Regenerating islet-derived protein 3 gamma (Reg3g) ameliorates tacrolimus-induced pancreatic β-cell dysfunction in mice by restoring mitochondrial function. In British journal of pharmacology, 179, 3078-3095. doi:10.1111/bph.15803. https://pubmed.ncbi.nlm.nih.gov/35060126/
6. Fan, Baochao, Zhou, Jinzhu, Zhao, Yongxiang, Fan, Huiying, Li, Bin. . Identification of Cell Types and Transcriptome Landscapes of Porcine Epidemic Diarrhea Virus-Infected Porcine Small Intestine Using Single-Cell RNA Sequencing. In Journal of immunology (Baltimore, Md. : 1950), 210, 271-282. doi:10.4049/jimmunol.2101216. https://pubmed.ncbi.nlm.nih.gov/36548460/
7. Xia, Fei, Cao, Hui, Du, Jiao, Liu, Yang, Xiang, Ming. 2015. Reg3g overexpression promotes β cell regeneration and induces immune tolerance in nonobese-diabetic mouse model. In Journal of leukocyte biology, 99, 1131-40. doi:10.1189/jlb.3A0815-371RRR. https://pubmed.ncbi.nlm.nih.gov/26667474/
8. Yin, Guoxiao, Du, Jiao, Cao, Hui, Xu, Qianqian, Xiang, Ming. 2015. Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis. In Digestive diseases and sciences, 60, 3656-68. doi:10.1007/s10620-015-3787-5. https://pubmed.ncbi.nlm.nih.gov/26182900/
9. Liu, Xiulan, Zhou, Zhongshi, Cheng, Qi, Ren, Hongyu, Xiang, Ming. 2017. Acceleration of pancreatic tumorigenesis under immunosuppressive microenvironment induced by Reg3g overexpression. In Cell death & disease, 8, e3033. doi:10.1038/cddis.2017.424. https://pubmed.ncbi.nlm.nih.gov/28880262/