Reg3g, also known as regenerating islet-derived 3 gamma, is an antimicrobial C-type lectin. It has been implicated in multiple biological functions. It acts both within the intestinal lumen and as a gut hormone, linking the intestinal microbiome to host physiology. It is involved in pathways related to energy balance, glucose regulation, and gut function. Its expression is regulated by factors like interleukin 22 (IL-22), and it may also play a role in the communication between injured axons and muscle during skeletal muscle and peripheral nerve regeneration [2,3].

In gene knockout studies, Reg3g knockout mice lack the beneficial effects on gut function, energy balance, and glucose regulation that are seen with high-inulin diets or vertical sleeve gastrectomy, which normally increase Reg3g expression. Also, in a model of alcoholic liver disease, engineered bacteria that produce IL-22 reduce liver damage by inducing Reg3g expression, but this effect is absent in Reg3g -/- mice. Additionally, in non-alcoholic steatohepatitis (NASH), Reg3g -/- mice show ileal barrier damage and endotoxin translocation, leading to liver inflammation and fibrosis [1,2,4].

In conclusion, Reg3g plays essential roles in maintaining gut-related physiological functions, glucose metabolism, and preventing certain liver diseases. Gene knockout mouse models have been crucial in revealing these functions, highlighting its potential as a therapeutic target for metabolic and liver-related diseases.

References:

1. Shin, Jae Hoon, Bozadjieva-Kramer, Nadejda, Shao, Yikai, Sandoval, Darleen A, Seeley, Randy J. 2022. The gut peptide Reg3g links the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function. In Cell metabolism, 34, 1765-1778.e6. doi:10.1016/j.cmet.2022.09.024. https://pubmed.ncbi.nlm.nih.gov/36240758/

2. Hendrikx, Tim, Duan, Yi, Wang, Yanhan, van Pijkeren, Jan-Peter, Schnabl, Bernd. 2018. Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice. In Gut, 68, 1504-1515. doi:10.1136/gutjnl-2018-317232. https://pubmed.ncbi.nlm.nih.gov/30448775/

3. 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/

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/