Upregulation of MiR-151-5p Promotes the Apoptosis of Intestinal Epithelial Cells by Targeting Brain-derived Neurotrophic Factor in Ulcerative Colitis Mice

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2022 Aug 8

PMID 35938703

Authors

Feng Zhou

Lipeng Chen

Shan Xu

Caijuan Si

Nan Li

Hui Dong

Peifen Zheng

Weifeng Wang

Affiliations

Soon will be listed here.

Abstract

Ulcerative colitis (UC) is the most prevalent form of chronic inflammatory bowel disease, the etiology of which is poorly understood. This study investigated the role of miR-151-5p on UC and explored the role of brain-derived neurotrophic factor (BDNF) in a UC mouse model and cell model. A UC mouse model was engineered by dextran sulfate sodium (DSS) induction. Primary mouse intestinal epithelial cells (IECs) were isolated. Colitis mice were intraperitoneally injected with miR-151-5p antagomir and antagomir negative control, and weight loss, disease activity index, and colon length of mice were measured. Colon tissues of mice were histologically analyzed. A UC cell model was constructed by treating MODE-K cells with DSS. miR-151-5p expression in the cell model was modulated by transfection. The exogenous BDNF effect on the UC cell model and intestinal cell apoptosis, viability and proliferation was detected by flow cytometry, CCK-8 and EdU experiment. The expression of miR-151-5p and apoptosis-related proteins was assessed through q-PCR and western blotting. miR-151-5p was upregulated in the colon tissues and primary IECs of colitis mice. miR-151-5p directly inhibited the expression of BNDF. miR-151-5p upregulation promoted apoptosis in UC MODE-K cells. miR-151-5p upregulation repressed the viability of UC MODE-K cells. Exogenous BNDF treatment reversed the effect of miR-151-5p on UC MODE-K cells. miR-151-5p knockdown improved UC symptoms in mice, including alleviating weight loss, reducing disease activity index and improving colon length and damaged colon tissues. miR-151-5p contributed to intestinal epithelial cells apoptosis in colitis mice via inhibiting BNDF expression.

Citing Articles

The Role and Mechanism of Retinol and Its Transformation Product, Retinoic Acid, in Modulating Oxidative Stress-Induced Damage to the Duck Intestinal Epithelial Barrier In Vitro.

Zhang L, Tang R, Wu Y, Liang Z, Liu J, Pi J Animals (Basel). 2023; 13(19).

PMID: 37835704 PMC: 10572057. DOI: 10.3390/ani13193098.

References

Modak J, Roy-OReilly M, Zhu L, Staff I, McCullough L . Differential MicroRibonucleic Acid Expression in Cardioembolic Stroke. J Stroke Cerebrovasc Dis. 2018; 28(1):121-124. PMC: 6625805. DOI: 10.1016/j.jstrokecerebrovasdis.2018.09.018. View

Gitter A, Wullstein F, Fromm M, Schulzke J . Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology. 2001; 121(6):1320-8. DOI: 10.1053/gast.2001.29694. View

Steinkamp M, Schulte N, Spaniol U, Pfluger C, Hartmann C, Kirsch J . Brain derived neurotrophic factor inhibits apoptosis in enteric glia during gut inflammation. Med Sci Monit. 2012; 18(4):BR117-22. PMC: 3560818. DOI: 10.12659/msm.882612. View

Zhang S, Ni W, Xiao M, Jiang F, Lu C, Wang R . Actin related protein 3 (ARP3) promotes apoptosis of intestinal epithelial cells in ulcerative colitis. Pathol Res Pract. 2018; 215(2):235-242. DOI: 10.1016/j.prp.2018.10.011. View

Li M, Zhang S, Qiu Y, He Y, Chen B, Mao R . Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3. Cell Death Dis. 2017; 8(3):e2699. PMC: 5386569. DOI: 10.1038/cddis.2017.76. View

Shkoda A, Ruiz P, Daniel H, Kim S, Rogler G, Sartor R . Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Gastroenterology. 2007; 132(1):190-207. DOI: 10.1053/j.gastro.2006.10.030. View

Earnshaw W, Martins L, Kaufmann S . Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem. 2000; 68:383-424. DOI: 10.1146/annurev.biochem.68.1.383. View

Han K, Jia N, Li J, Yang L, Min L . Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer's disease. Mol Med Rep. 2013; 8(3):737-40. PMC: 3782531. DOI: 10.3892/mmr.2013.1601. View

Gillen C, Walmsley R, Prior P, Andrews H, Allan R . Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut. 1994; 35(11):1590-2. PMC: 1375617. DOI: 10.1136/gut.35.11.1590. View

10.

Wang J, Dong L, Wang M, Guo J, Zhao Y . MiR-146a regulates the development of ulcerative colitis via mediating the TLR4/MyD88/NF-κB signaling pathway. Eur Rev Med Pharmacol Sci. 2019; 23(5):2151-2157. DOI: 10.26355/eurrev_201903_17260. View

11.

Amasheh S, Meiri N, Gitter A, Schoneberg T, Mankertz J, Schulzke J . Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci. 2002; 115(Pt 24):4969-76. DOI: 10.1242/jcs.00165. View

12.

Liu S, Zhang S, Lv X, Lu J, Ren C, Zeng Z . Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway. Int Immunopharmacol. 2019; 75:105768. DOI: 10.1016/j.intimp.2019.105768. View

13.

Xu X, Zhu X, Wang C, Li Y, Fan C, Kao X . microRNA-650 promotes inflammation induced apoptosis of intestinal epithelioid cells by targeting NLRP6. Biochem Biophys Res Commun. 2019; 517(4):551-556. DOI: 10.1016/j.bbrc.2019.06.077. View

14.

Zhao D, Zhang W, Qi Q, Long X, Li X, Yu Y . Brain-derived neurotrophic factor modulates intestinal barrier by inhibiting intestinal epithelial cells apoptosis in mice. Physiol Res. 2018; 67(3):475-485. DOI: 10.33549/physiolres.933641. View

15.

Lu X, Yu Y, Tan S . The role of the miR-21-5p-mediated inflammatory pathway in ulcerative colitis. Exp Ther Med. 2020; 19(2):981-989. PMC: 6966149. DOI: 10.3892/etm.2019.8277. View

16.

Bing X, Xuelei L, Wanwei D, Linlang L, Keyan C . EGCG Maintains Th1/Th2 Balance and Mitigates Ulcerative Colitis Induced by Dextran Sulfate Sodium through TLR4/MyD88/NF-B Signaling Pathway in Rats. Can J Gastroenterol Hepatol. 2018; 2017:3057268. PMC: 5748319. DOI: 10.1155/2017/3057268. View

17.

Chiyomaru T, Yamamura S, Zaman M, Majid S, Deng G, Shahryari V . Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151. PLoS One. 2012; 7(8):e43812. PMC: 3426544. DOI: 10.1371/journal.pone.0043812. View

18.

Chu X, Wang J, Chen G, Zhang G, Zhang D, Cai Y . Overexpression of microRNA-495 improves the intestinal mucosal barrier function by targeting STAT3 via inhibition of the JAK/STAT3 signaling pathway in a mouse model of ulcerative colitis. Pathol Res Pract. 2017; 214(1):151-162. DOI: 10.1016/j.prp.2017.10.003. View

19.

Jiang W, Han Y, Hu M, Bao X, Yan Y, Chen G . A study on regulatory mechanism of miR-223 in ulcerative colitis through PI3K/Akt-mTOR signaling pathway. Eur Rev Med Pharmacol Sci. 2019; 23(11):4865-4872. DOI: 10.26355/eurrev_201906_18074. View

20.

Paraskevi A, Theodoropoulos G, Papaconstantinou I, Mantzaris G, Nikiteas N, Gazouli M . Circulating MicroRNA in inflammatory bowel disease. J Crohns Colitis. 2012; 6(9):900-4. DOI: 10.1016/j.crohns.2012.02.006. View