miRNA介导应激幼畜肠道损伤的研究进展

doi:10.11843/j.issn.0366-6964.2023.03.003

摘要/Abstract

摘要： 随着畜牧业的飞速发展，集约化饲养、幼畜早期断奶策略应运而生，同时各种应激(如：热应激、冷应激、断奶应激、运输应激、氧化应激)增加，导致免疫系统还未完全建立的幼畜肠道损伤，严重时危及生命。miRNA是一类可调控基因表达的内源性非编码单链小分子RNA，是基因家族的重要成员，参与机体内部几乎所有的信号通路，能够调控肠上皮细胞的增殖与分化，介导肠黏膜屏障损伤。本文综述了应激对肠黏膜屏障功能的影响，miRNA对幼畜肠黏膜屏障功能的调控作用及可能作用途径。同时，综述了miRNA参与外源添加剂作用的模式，为营养素靶向干预调控幼畜肠道免疫功能提供理论依据，对提高幼畜培育具有重要意义。

关键词: 应激, miRNA, 肠黏膜屏障

Abstract: With the rapid development of animal husbandry, intensive feeding and early weaning strategy comes into being. At the same time, all kinds of stress (such as heat stress, cold stress, weaning stress, transport stress, oxidative stress) increase, resulting in intestine injury of young farm animals whose immune system has not been fully established, which is life-threatening in serious cases. miRNA is a kind of endogenous non-coding single-stranded small RNA, which can regulate gene expression. As an important member of the gene family, miRNA was involved in almost all the signaling pathways in the body. miRNA could regulate the proliferation and differentiation of intestinal epithelial cells and mediate intestinal mucosal barrier injury. This review summarized the effect of stress on intestinal mucosal barrier function, the regulatory role and possible pathways of miRNA on intestinal mucosal barrier function of young farm animals. At the same time, the mode of miRNA participating in the action of exogenous additives was reviewed to provide a theoretical basis for nutrients targeted intervention to regulate the intestinal immune function of young farm animals, and was of great significance to improve the breeding of young farm animals.

Key words: stress, miRNA, intestinal mucosal barrier

中图分类号:

S813
S815.7

韩露露, 韩德平, 赵启南, 刁其玉, 崔凯. miRNA介导应激幼畜肠道损伤的研究进展[J]. 畜牧兽医学报, 2023, 54(3): 877-888.

HAN Lulu, HAN Deping, ZHAO Qinan, DIAO Qiyu, CUI Kai. Research Progress of Intestinal Injury in Young Farm Animals under Stress Mediated by miRNA[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 877-888.

参考文献 89

[1]	CHAUHAN S S,RASHAMOL V P,BAGATH M,et al.Impacts of heat stress on immune responses and oxidative stress in farm animals and nutritional strategies for amelioration[J].Int J Biometeorol,2021,65(7):1231-1244.
[2]	BAGATH M,KRISHNAN G,DEVARAJ C,et al.The impact of heat stress on the immune system in dairy cattle:A review[J].Res Vet Sci,2019,126:94-102.
[3]	NOVAIS A K,DESCHÊNE K,MARTEL-KENNES Y,et al.Weaning differentially affects mitochondrial function,oxidative stress,inflammation and apoptosis in normal and low birth weight piglets[J].PLoS One,2021,16(2):e0247188.
[4]	GE J,LI H,SUN F,et al.Transport stress-induced cerebrum oxidative stress is not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks[J].J Anim Sci,2017,95(7):2871-2878.
[5]	KOCH F,THOM U,ALBRECHT E,et al.Heat stress directly impairs gut integrity and recruits distinct immune cell populations into the bovine intestine[J].Proc Natl Acad Sci U S A,2019,116(21):10333-10338.
[6]	MOESER A J,POHL C S,RAJPUT M.Weaning stress and gastrointestinal barrier development:implications for lifelong gut health in pigs[J].Anim Nutr,2017,3(4):313-321.
[7]	POHL C S,MEDLAND J E,MACKEY E,et al.Early weaning stress induces chronic functional diarrhea,intestinal barrier defects,and increased mast cell activity in a porcine model of early life adversity[J].Neurogastroenterol Motil,2017,29(11):e13118.
[8]	BARTEL D P.Metazoan microRNAs[J].Cell,2018,173(1):20-51.
[9]	CHEN L,HEIKKINEN L,WANG C L,et al.Trends in the development of miRNA bioinformatics tools[J].Brief Bioinform,2019,20(5):1836-1852.
[10]	EARLEY H,LENNON G,BALFEÁ,et al.The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis[J].Sci Rep,2019,9(1):15683.
[11]	SCHÖNAUEN K,LE N,VON ARNIM U,et al.Circulating and fecal microRNAs as biomarkers for inflammatory bowel diseases[J].Inflamm Bowel Dis,2018,24(7):1547-1557.
[12]	MAHURKAR-JOSHI S,RANKIN C R,VIDELOCK E J,et al.The colonic mucosal microRNAs,microRNA-219a-5p,and microRNA-338-3p are downregulated in irritable bowel syndrome and are associated with barrier function and MAPK signaling[J].Gastroenterology,2021,160(7):2409-2422.e19.
[13]	MOMEN-HERAVI F,BALA S.miRNA regulation of innate immunity[J].J Leukoc Biol,2018,103(6):1205-1217.
[14]	ENGEDAL N,ŽEROVNIK E,RUDOV A,et al.From oxidative stress damage to pathways,networks,and autophagy via microRNAs[J].Oxid Med Cell Longev,2018,2018:4968321.
[15]	RANI V,SENGAR R S.Biogenesis and mechanisms of microRNA-mediated gene regulation[J].Biotechnol Bioeng,2022,119(3):685-692.
[16]	KHVOROVA A,REYNOLDS A,JAYASENA S D.Functional siRNAs and miRNAs exhibit strand bias[J].Cell,2003,115(2):209-216.
[17]	SAWERA M,GORODKIN J,CIRERA S,et al.Mapping and expression studies of the mir17-92 cluster on pig chromosome 11[J].Mamm Genome,2005,16(8):594-598.
[18]	DAVIS E,CAIMENT F,TORDOIR X,et al.RNAi-mediated allelic trans-interaction at the imprinted Rtl1/Peg11 locus[J].Curr Biol,2005,15(8):743-749.
[19]	XU H T,WANG X B,DU Z L,et al.Identification of microRNAs from different tissues of chicken embryo and adult chicken[J].FEBS Lett,2006,580(15):3610-3616.
[20]	COUTINHO L L,MATUKUMALLI L K,SONSTEGARD T S,et al.Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues[J].Physiol Genomics,2007,29(1):35-43.
[21]	TONG H L,JIANG R Y,LIU T T,et al.bta-miR-378 promote the differentiation of bovine skeletal muscle-derived satellite cells[J].Gene,2018,668:246-251.
[22]	LIAO R R,LV Y H,ZHU L H,et al.Altered expression of miRNAs and mRNAs reveals the potential regulatory role of miRNAs in the developmental process of early weaned goats[J].PLoS One,2019,14(8):e0220907.
[23]	IQBAL A,PING J,ALI S,et al.Role of microRNAs in myogenesis and their effects on meat quality in pig-A review[J].Asian-Australas J Anim Sci,2020,33(12):1873-1884.
[24]	WANG X G,YU J F,ZHANG Y,et al.Identification and characterization of microRNA from chicken adipose tissue and skeletal muscle[J].Poult Sci,2012,91(1):139-149.
[25]	HONG L J,LIU R Z,QIAO X W,et al.Differential microRNA expression in porcine endometrium involved in remodeling and angiogenesis that contributes to embryonic implantation[J].Front Genet,2019,10:661.
[26]	DONADEU F X,SANCHEZ J M,MOHAMMED B T,et al.Relationships between size,steroidogenesis and miRNA expression of the bovine corpus luteum[J].Theriogenology,2020,145:226-230.
[27]	TAO X,LIU S J,MEN X,et al.Over-expression of miR-146b and its regulatory role in intestinal epithelial cell viability,proliferation,and apoptosis in piglets[J].Biol Direct,2017,12(1):27.
[28]	QI X F,LI Z,LI H,et al.MicroRNA-1 negatively regulates peripheral NK cell function via Tumor Necrosis Factor-like Weak Inducer of Apoptosis (TWEAK) signaling pathways during PPRV infection[J].Front Immunol,2020,10:3066.
[29]	SHARBATI-TEHRANI S,KUTZ-LOHROFF B,BERGBAUER R,et al.miR-Q:A novel quantitative RT-PCR approach for the expression profiling of small RNA molecules such as miRNAs in a complex sample[J].BMC Mol Biol,2008,9:34.
[30]	HOU L,JI Z B,WANG G Z,et al.Identification and characterization of microRNAs in the intestinal tissues of sheep (Ovis aries)[J].PLoS One,2018,13(2):e0193371.
[31]	LIAN P Q,BRABER S,VARASTEH S,et al.Hypoxia and heat stress affect epithelial integrity in a Caco-2/HT-29 co-culture[J].Sci Rep,2021,11(1):13186.
[32]	LAM S,BAI X W,SHKOPOROV A N,et al.Roles of the gut virome and mycobiome in faecal microbiota transplantation[J].Lancet Gastroenterol Hepatol,2022,7(5):472-484.
[33]	HARRIS L A,BAFFY N.Modulation of the gut microbiota:A focus on treatments for irritable bowel syndrome[J].Postgrad Med,2017,129(8):872-888.
[34]	CAO Q Q,LIN L X,XU T T,et al.Aflatoxin B1 alters meat quality associated with oxidative stress,inflammation,and gut-microbiota in sheep[J].Ecotoxicol Environ Saf,2021,225:112754.
[35]	JOHANSSON M E V,HANSSON G C.Immunological aspects of intestinal mucus and mucins[J].Nat Rev Immunol,2016,16(10):639-649.
[36]	KWON M S,CHUNG H K,XIAO L,et al.MicroRNA-195 regulates Tuft cell function in the intestinal epithelium by altering translation of DCLK1[J].Am J Physiol Cell Physiol,2021,320(6):C1042-C1054.
[37]	HAN L L,TAO H,KANG L Y,et al.Transcriptome and iTRAQ-Based proteome reveal the molecular mechanism of intestinal injury induced by weaning Ewe's milk in lambs[J].Front Vet Sci,2022,9:809188.
[38]	LIU L,WU C M,CHEN D W,et al.Selenium-enriched yeast alleviates oxidative stress-induced intestinal mucosa disruption in weaned pigs[J].Oxid Med Cell Longev,2020,2020:5490743.
[39]	王亚芳.黄芪甲苷对犊牛抗氧化功能的影响及其作用机制的研究[D].济南:山东师范大学,2020.WANG Y F.Research about the effect of Astragaloside IV on antioxidant function and correlative action mechanism of calves[D].Jinan:Shandong Normal University,2020.(in Chinese)
[40]	CAO S T,WANG C C,WU H,et al.Weaning disrupts intestinal antioxidant status,impairs intestinal barrier and mitochondrial function,and triggers mitophagy in piglets[J].J Anim Sci,2018,96(3):1073-1083.
[41]	FRANCO L M,GADKARI M,HOWE K N,et al.Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses[J].J Exp Med,2019,216(2):384-406.
[42]	ZHANG Q,LI C,NIU X L,et al.An intensive milk replacer feeding program benefits immune response and intestinal microbiota of lambs during weaning[J].BMC Vet Res,2018,14(1):366.
[43]	BHATTACHARYYA A,CHATTOPADHYAY R,MITRA S,et al.Oxidative stress:An essential factor in the pathogenesis of gastrointestinal mucosal diseases[J].Physiol Rev,2014,94(2):329-354.
[44]	PÉREZ-REYTOR D,JAÑA V,PAVEZ L,et al.Accessory toxins of Vibrio pathogens and their role in epithelial disruption during infection[J].Front Microbiol,2018,9:2248.
[45]	VECCHIO A J,STROUD R M.Claudin-9 structures reveal mechanism for toxin-induced gut barrier breakdown[J].Proc Natl Acad Sci U S A,2019,116(36):17817-17824.
[46]	SINGH N,SHIRDEL E A,WALDRON L,et al.The murine caecal microRNA signature depends on the presence of the endogenous microbiota[J].Int J Biol Sci,2012,8(2):171-186.
[47]	LI M H,CHEN W D,WANG Y D.The roles of the gut microbiota-miRNA interaction in the host pathophysiology[J].Mol Med,2020,26(1):101.
[48]	WU Z C,QIN W Y,WU S,et al.Identification of microRNAs regulating Escherichia coli F18 infection in Meishan weaned piglets[J].Biol Direct,2016,11(1):59.
[49]	SABHARWAL H,CICHON C,ÖLSCHLÄGER T A,et al.Interleukin-8,CXCL1,and MicroRNA miR-146a responses to probiotic Escherichia coli Nissle 1917 and Enteropathogenic E.coli in human intestinal epithelial T84 and Monocytic THP-1 cells after apical or Basolateral infection[J].Infect Immun,2016,84(9):2482-2492.
[50]	KREUZER-REDMER S,BEKURTZ J C,ARENDS D,et al.Feeding of Enterococcus faecium NCIMB 10415 leads to intestinal miRNA-423-5p-Induced regulation of immune-relevant genes[J].Appl Environ Microbiol,2016,82(8):2263-2269.
[51]	JIANG S,LI X,WANG X H,et al.MicroRNA profiling of the intestinal tissue of Kazakh sheep after experimental Echinococcus granulosus infection,using a high-throughput approach[J].Parasite,2016,23:23.
[52]	WANG O,ZHOU M,CHEN Y H,et al.MicroRNAomes of cattle intestinal tissues revealed possible miRNA regulated mechanisms involved in Escherichia coli O157 fecal shedding[J].Front Cell Infect Microbiol,2021,11:634505.
[53]	ZHAO Y,ZENG D,WANG H S,et al.Analysis of miRNA expression in the ileum of broiler chickens during Bacillus licheniformis H2 supplementation against subclinical necrotic enteritis[J].Probiotics Antimicro Prot,2021,13(2):356-366.
[54]	OSHIMA T,MIWA H.Gastrointestinal mucosal barrier function and diseases[J].J Gastroenterol,2016,51(8):768-778.
[55]	石凯歌,段志军.大黄素修复肠屏障的研究进展[J].中华中医药学刊,2021,39(9):130-133.SHI K G,DUAN Z J.Research progress of Emodin in repair of intestinal barriers[J].Chinese Archives of Traditional Chinese Medicine,2021,39(9):130-133.(in Chinese)
[56]	HE S S,GUO Y H,ZHAO J X,et al.Ferulic acid ameliorates lipopolysaccharide-induced barrier dysfunction via microRNA-200c-3p-mediated activation of PI3K/AKT pathway in Caco-2 Cells[J].Front Pharmacol,2020,11:376.
[57]	YAO D B,DAI W L,DONG M,et al.MUC2 and related bacterial factors:Therapeutic targets for ulcerative colitis[J].eBioMedicine,2021,74:103751.
[58]	GOTO Y,KIYONO H.Epithelial cell microRNAs in gut immunity[J].Nat Immunol,2011,12(3):195-197.
[59]	HUANG L,SUN T Y,HU L J,et al.Elevated miR-124-3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T-synthase[J].Aging Cell,2020,19(11):e13252.
[60]	SUN T Y,LI Y Q,ZHAO F Q,et al.miR-1-3p and miR-124-3p synergistically damage the intestinal barrier in the ageing colon[J].J Crohns Colitis,2022,16(4):656-667.
[61]	ZHANG H,CHEN F,LIANG Z H,et al.Analysis of miRNAs and their target genes associated with mucosal damage caused by transport stress in the mallard duck intestine[J].PLoS One,2020,15(8):e0237699.
[62]	WU S,PAN L J,LIAO H F,et al.High-fat diet increased NADPH-oxidase-related oxidative stress and aggravated LPS-induced intestine injury[J].Life Sci,2020,253:117539.
[63]	LIU Z,TIAN Y,JIANG Y,et al.Protective effects of let-7b on the expression of occludin by targeting P38 MAPK in preventing intestinal barrier dysfunction[J].Cell Physiol Biochem,2018,45(1):343-355.
[64]	TAO X,XU Z W.MicroRNA transcriptome in swine small intestine during weaning stress[J].PLoS One,2013,8(11):e79343.
[65]	LI Q L,YANG C H,DU J,et al.Characterization of miRNA profiles in the mammary tissue of dairy cattle in response to heat stress[J].BMC Genomics,2018,19(1):975.
[66]	NAJM A,MASSON F M,PREUSS P,et al.MicroRNA-17-5p reduces inflammation and bone erosions in mice with Collagen-induced arthritis and directly targets the JAK/STAT pathway in rheumatoid arthritis Fibroblast-like synoviocytes[J].Arthritis Rheumatol,2020,72(12):2030-2039.
[67]	YUE J N,LI W M,HONG W Z,et al.miR-210 inhibits apoptosis of vascular endothelial cells via JAK-STAT in arteriosclerosis obliterans[J].Eur Rev Med Pharmacol Sci,2019,23(3 Suppl):319-326.
[68]	王莉.黄芩苷通过microRNA对TNF-α诱导的肠上皮细胞通透性的保护机制[D].广州:广州中医药大学,2017.WANG L.Baicalin protects against TNF-α-induced injury by regulating microRNA in IEC-6 cells[D].Guangzhou:Guangzhou University of Chinese Medicine,2017.(in Chinese)
[69]	ZHAO X J,LI J J,MA J J,et al.miR-124a mediates the impairment of intestinal epithelial integrity by targeting aryl hydrocarbon receptor in Crohn's disease[J].Inflammation,2020,43(5):1862-1875.
[70]	LIU Z H,LI C,CHEN S H,et al.MicroRNA-21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier dysfunction[J].J Cell Biochem,2019,120(3):4545-4554.
[71]	PAN F,TANG W,ZHOU Z,et al.Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease[J].Lupus,2018,27(12):1898-1902.
[72]	MICHAUD E,MASTRANDREA C,ROCHEREAU N,et al.Human secretory IgM:an elusive player in mucosal immunity[J].Trends Immunol,2020,41(2):141-156.
[73]	SHACKLETT B L.Mucosal immunity in HIV/SIV infection:T Cells,B cells and beyond[J].Curr Immunol Rev,2019,15(1):63-75.
[74]	CHANG C S,KAO C Y.Current understanding of the gut microbiota shaping mechanisms[J].J Biomed Sci,2019,26(1):59.
[75]	BIOLATTI B,BOLLO E,CANNIZZO F T,et al.Effects of low-dose dexamethasone on thymus morphology and immunological parameters in veal calves[J].J Vet Med A Physiol Pathol Clin Med,2005,52(4):202-208.
[76]	DO D N,DUDEMAINE P L,FOMENKY B E,et al.Integration of miRNA and mRNA co-expression reveals potential regulatory roles of miRNAs in developmental and immunological processes in calf ileum during early growth[J].Cells,2018,7(9):134.
[77]	CHEN L,GAO D,SHAO Z Z,et al.miR-155 indicates the fate of CD4+ T cells[J].Immunol Lett,2020,224:40-49.
[78]	GAO X L,HUANG X Y,YANG Q L,et al.MicroRNA-21-5p targets PDCD4 to modulate apoptosis and inflammatory response to Clostridium perfringens beta2 toxin infection in IPEC-J2 cells[J].Dev Comp Immunol,2021,114:103849.
[79]	PHAM T T,BAN J,HONG Y,et al.MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis[J].Vet Res,2020,51(1):8.
[80]	SAWANT D V,WU H,KAPLAN M H,et al.The Bcl6 target gene microRNA-21 promotes Th2 differentiation by a T cell intrinsic pathway[J].Mol Immunol,2013,54(3-4):435-442.
[81]	MIKAMI Y,PHILIPS R L,SCIUMÈ G,et al.MicroRNA-221 and-222 modulate intestinal inflammatory Th17 cell response as negative feedback regulators downstream of interleukin-23[J].Immunity,2021,54(3):514-525.e6.
[82]	YAO L,YAN H.MiR-182 inhibits oxidative stress and epithelial cell apoptosis in lens of cataract rats through PI3K/Akt signaling pathway[J].Eur Rev Med Pharmacol Sci,2020,24(23):12001-12008.
[83]	GRAVES D T,MILOVANOVA T N.Mucosal immunity and the FOXO1 transcription factors[J].Front Immunol,2019,10:2530.
[84]	COFFRE M,BENHAMOU D,RIEβ D,et al.miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation[J].Cell Rep,2016,17(9):2271-2285.
[85]	WILLIAMS D L,HA T Z,LI C F,et al.Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality[J].Crit Care Med,2003,31(6):1808-1818.
[86]	CHELESCHI S,TENTI S,MONDANELLI N,et al.MicroRNA-34a and microRNA-181a mediate Visfatin-induced apoptosis and oxidative stress via NF-κB pathway in human osteoarthritic chondrocytes[J].Cells,2019,8(8):874.
[87]	LV Z C,CAO X Y,GUO Y X,et al.Effects of MiR-146a on repair and inflammation in rats with spinal cord injury through the TLR/NF-κB signaling pathway[J].Eur Rev Med Pharmacol Sci,2019,23(11):4558-4563.
[88]	CAO Y X,GUO Y K,ZONG R K,et al.Drug-containing serum of Xinfeng capsules protect against H9C2 from death by enhancing miRNA-21 and inhibiting toll-like receptor 4/phosphorylated p-38(p-p38)/p-p65 signaling pathway and proinflammatory cytokines expression[J].J Tradit Chin Med,2018,38(3):359-365.
[89]	谢春燕,谢刚,季语竹.柚皮素通过miR-22抑制NLRP3炎症小体并减轻溃疡性结肠炎大鼠模型肠屏障损伤[J].中国病理生理杂志,2021,37(9):1573-1581.XIE C Y,XIE G,JI Y Z.Naringenin inhibits NLRP3 inflammasome through miR-22 and reduces intestinal barrier damage in a rat model of ulcerative colitis[J].Chinese Journal of Pathophysiology,2021,37(9):1573-1581.(in Chinese)