Chen Xintong,Jiang Weiwei.Research advances in Reg3g-mediated regulation of intestinal homeostasis[J].Journal of Clinical Pediatric Surgery,,():689-692.[doi:10.3760/cma.j.cn101785-202401067]
Research advances in Reg3g-mediated regulation of intestinal homeostasis
- Abstract:
- Regenerating islet-derived protein 3 gamma (Reg3g) is a calcium-independent C-type lectin-like antimicrobial protein.It contributes to the maintenance of intestinal homeostasis through modulating the composition of gut microbiota,preserving spatial segregation between microbiota and intestinal mucosa,regulating inflammatory responses and promoting epithelial barrier repair.Short bowel syndrome (SBS) is manifested by a marked reduction in functional intestinal absorptive surface area after extensive small bowel resection,intestinal exclusion or congenital intestinal shortening,resulting in disorders of nutrient,water and electrolyte absorption.SBS children present frequently with gut dysbiosis,mucosal inflammation and impaired barrier function.Therefore Reg3g-mediated regulation of intestinal homeostasis may provide a potential therapeutic target for improving intestinal barrier dysfunction and microbial imbalance in pediatric SBS.This review summarized the structural characteristics of Reg3g and discussed its role in intestinal homeostasis and the related signaling pathways.
References:
[1] Wan TT,Wang YL,He KX,et al.Microbial sensing in the intestine[J].Protein Cell,2023,14(11):824-860.DOI:10.1093/procel/pwad028.
[2] Hu YY,Li Y,Zhang Q,et al.The AMP-antibiotic-microbiota triad in IBD:a mechanistic framework for dysregulated antimicrobial defense[J].Front Immunol,2026,17:1779550.DOI:10.3389/fimmu.2026.1779550.
[3] Shin JH,Bozadjieva-Kramer N,Seeley RJ.Reg3γ:current understanding and future therapeutic opportunities in metabolic disease[J].Exp Mol Med,2023,55(8):1672-1677.DOI:10.1038/s12276-023-01054-5.
[4] Qi ZY,Pang WF,Zha X,et al.REG/Reg family proteins:mediating gut microbiota homeostasis and implications in digestive diseases[J].Gut Microbes,2025,17(1):2568055.DOI:10.1080/19490976.2025.2568055.
[5] 邹婵娟,李波,董洁,等.新生儿肠闭锁合并胎粪性腹膜炎患儿并发短肠综合征的临床特征分析[J].临床小儿外科杂志,2024,23(12):1144-1148.DOI:10.3760/cma.j.cn101785-202308020-007. Zou CJ,Li B,Dong J,et al.Analysis of clinical features of neonatal intestinal atresia complicated with meconium peritonitis in children of short bowel syndrome[J].J Clin Ped Sur,2024,23(12):1144-1148.DOI:10.3760/cma.j.cn101785-202308020-007.
[6] Terazono K,Yamamoto H,Takasawa S,et al.A novel gene activated in regenerating islets[J].J Biol Chem,1988,263(5):2111-2114.DOI:10.1016/S0021-9258(18)69176-8.
[7] Liao F,Xiao X.The Reg gene family:roles in gastric and colorectal cancer progression and its potential for targeted therapy[J].Horm Cancer,2025,16(1):2044.DOI:10.1007/s12672-025-03881-6.
[8] Wang LY,Quan YC,Zhu YX,et al.The regenerating protein 3A:a crucial molecular with dual roles in cancer[J].Mol Biol Rep,2022,49(2):1491-1500.DOI:10.1007/s11033-021-06904-x.
[9] Mukherjee S,Partch CL,Lehotzky RE,et al.Regulation of C-type lectin antimicrobial activity by a flexible n-terminal prosegment[J].J Biol Chem,2009,284(8):4881-4888.DOI:10.1074/jbc.M808077200.
[10] Ra YE,Bang YJ.Balancing act of the intestinal antimicrobial proteins on gut microbiota and health[J].J Microbiol,2024,62(3):167-179.DOI:10.1007/s12275-024-00122-3.
[11] Faivre J,Shalhoub H,Nguyen TS,et al.REG3A:a multifunctional antioxidant lectin at the crossroads of microbiota regulation,inflammation,and cancer[J].Cancers (Basel),2025,17(14):2395.DOI:10.3390/cancers17142395.
[12] Vaishnava S,Yamamoto M,Severson KM,et al.The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine[J].Science,2011,334(6053):255-258.DOI:10.1126/science.1209791.
[13] Natividad JMM,Hayes CL,Motta JP,et al.Differential induction of antimicrobial REGIII by the intestinal microbiota and Bifidobacterium breve NCC2950[J].Appl Environ Microbiol,2013,79(24):7745-7754.DOI:10.1128/AEM.02470-13.
[14] Loonen LMP,Stolte EH,Jaklofsky MTJ,et al.REG3γ-deficient mice have altered mucus distribution and increased mucosal inflammatory responses to the microbiota and enteric pathogens in the ileum[J].Mucosal Immunol,2014,7(4):939-947.DOI:10.1038/mi.2013.109.
[15] Arumugam P,Saha K,Nighot P.Intestinal epithelial tight junction barrier regulation by novel pathways[J].Inflamm Bowel Dis,2025,31(1):259-271.DOI:10.1093/ibd/izae232.
[16] Zhao DC,Kim YH,Jeong S,et al.Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease[J].J Clin Invest,2018,128(11):4970-4979.DOI:10.1172/JCI99261.
[17] McMahan RH,Najarro KM,Giesy LE,et al.Intestinal REG3G protects against gastrointestinal dysfunction in a murine model of ethanol intoxication and burn injury[J].Shock,2026,65(3):528-537.DOI:10.1097/SHK.0000000000002737.
[18] Hendrikx T,Duan Y,Wang YH,et al.Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice[J].Gut,2019,68(8):1504-1515.DOI:10.1136/gutjnl-2018-317232.
[19] Brooks JF 2nd,Behrendt CL,Ruhn KA,et al.The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock[J].Cell,2021,184(16):4154-4167.e12.DOI:10.1016/j.cell.2021.07.001.
[20] Gong JF,Xu JY,Zhu WM,et al.Epithelial-specific blockade of MyD88-dependent pathway causes spontaneous small intestinal inflammation[J].Clin Immunol,2010,136(2):245-256.DOI:10.1016/j.clim.2010.04.001.
[21] Hilberath J,Busch A,Schoppmeier U,et al.Small intestinal bacterial overgrowth and dysbiosis in children with intestinal failure:a descriptive cohort study[J].JPEN J Parenter Enteral Nutr,2025,49(8):964-974.DOI:10.1002/jpen.2808.
[22] Cleminson JS,Young GR,Campbell DI,et al.Gut microbiome in paediatric short bowel syndrome:a systematic review and sequencing re-analysis[J].Pediatr Res,2025,98(6):2082-2086.DOI:10.1038/s41390-025-04083-0.
[23] Velimirovic M,Osterman V,Prislan A,et al.Small intestinal bacterial overgrowth in children with short bowel syndrome:risk factors,clinical presentation and management-a single-center experience[J].Children (Basel),2025,12(3):351.DOI:10.3390/children12030351.
Memo
收稿日期:2024-1-30。
基金项目:江苏省卫健委面上项目(2022037);江苏省卫健委高层次卫生人才"六个一工程"拔尖人才项目资助(GY2020019)
通讯作者:蒋维维,Email:wwjiang@njmu.edu.cn