Objective: To detect differentially expressed miRNAs in exosomes derived from intestinal epithelial cells of essential hypertensive rats, and to enrich and analyze their target genes. Methods: Three Spontaneously hypertensive rats (SHR) and three Wistar-Kyoto rats (WKY) were selected as the research objects. The expression of miRNA in exosomes derived from intestinal epithelial cells of rats was detected by high-throughput sequencing. The differentially expressed miRNAs in the two groups of rats were screened and their target genes were predicted. The target genes were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) using biological function software. Results: Compared with the WKY group, there were 37 differentially expressed miRNAs in the SHR group (All P<0.05), 32 miRNAs were up-regulated and 5 miRNAs were down-regulated. Among them, rno-miR-208b-3p, rno-miR-134-5p, rno-miR-93-3p, rno-miR-378b, rno-miR-96-5p, rno-miR-210-3p, and rno-miR-208a-3p were noteworthy. A total of 10 662 miRNA downstream target genes were predicted, and a total of 34 127 target sites were predicted. GO enrichment was mainly concentrated in membrane-bound organelles, protein binding, and positively regulated biological processes. KEGG enrichment was mainly concentrated in MAPK, mTOR, Ras and TNF signaling pathways. Conclusion: The expression of miRNA in exosomes derived from intestinal epithelial cells of essential hypertensive rats was significantly different. Its target genes may be involved in MAPK, mTOR, Ras and TNF signaling pathways through cell growth and differentiation, angiogenesis and metabolic function, thus affecting the occurrence and development of hypertensive diseases.
[1] Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies[J]. Lancet, 2002, 360(9349): 1903-1913.
[2] Pugh D, Dhaun N. Hypertension and vascular inflammation: another piece of the genetic puzzle[J]. Hypertension, 2021, 77(1): 190-192.
[3] Mcmaster WG, Kirabo A, Madhur MS, et al. Inflammation, immunity, and hypertensive end-organ damage[J]. Circ Res, 2015, 116(6): 1022-1033.
[4] Li X, Wei YX, Wang ZG. MicroRNA-21 and hypertension[J]. Hypertens Res, 2018, 41(9): 649-661.
[5] Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of hypertension: the mosaic theory and beyond[J]. Circ Res, 2021, 128(7): 847-863.
[6] Ohshima K, Inoue K, Fujiwara A, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line[J]. PLoS One, 2010, 5(10): e13247.
[7] Miranda KC, Bond DT, Mckee M, et al. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease[J]. Kidney Int, 2010, 78(2): 191-199.
[8] Zheng D, Huo M, Li B, et al. The role of exosomes and exosomal microRNA in cardiovascular disease[J]. Front Cell Dev Biol, 2020, 8: 616161.
[9] Osada-Oka M, Shiota M, Izumi Y, et al. Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions[J]. Hypertens Res, 2017, 40(4): 353-360.
[10] Shibata H. Exosomes and exosomal cargo in urinary extracellular vesicles: novel potential biomarkers for mineralocorticoid-receptor-associated hypertension[J]. Hypertens Res, 2021, 44(12): 1668-1670.
[11] Lam B, Nwadozi E, Haas TL, et al. High glucose treatment limits drosha protein expression and alters AngiomiR maturation in microvascular primary endothelial cells via an Mdm2-dependent mechanism[J]. Cells, 2021, 10(4):742.
[12] Wang JF, Zhang JJ, Ding XF, et al. Differential microRNA expression profiles and bioinformatics analysis between young and aging spontaneously hypertensive rats[J]. Int J Mol Med, 2018, 41(3): 1584-1594.
[13] Zhang XY, Wang XY, Wu J, et al. The diagnostic values of circulating miRNAs for hypertension and bioinformatics analysis[J]. Biosci Rep, 2018, 38(4):BSR20180525.
[14] Tian L, Cai DH, Zhuang DR, et al. MiR-96-5p regulates proliferation, migration, and apoptosis of vascular smooth muscle cell induced by angiotensin Ⅱ via targeting NFAT5[J]. J Vasc Res, 2020, 57(2): 86-96.
[15] Guarner-Lans V, Ramírez-Higuera A, Rubio-Ruiz ME, et al. Early programming of adult systemic essential hypertension[J]. Int J Mol Sci, 2020, 21(4):1203.
[16] Orlov SN, Dam TV, Tremblay J, et al. Apoptosis in vascular smooth muscle cells: role of cell shrinkage[J]. Biochem Biophys Res Commun, 1996, 221(3): 708-715.
[17] Chen TJ, Sun MR, Zhou QY, et al. Extracellular vesicles derived from endothelial cells in hypoxia contribute to pulmonary artery smooth muscle cell proliferation in-vitro and pulmonary hypertension in mice[J]. Pulm Circ, 2022, 12(1): e12014.
[18] Jia GH, Sowers JR. Hypertension in diabetes: an update of basic mechanisms and clinical disease[J]. Hypertension, 2021, 78(5): 1197-1205.
[19] Liu W, Cao HC, Ye C, et al. Hepatic miR-378 targets p110α and controls glucose and lipid homeostasis by modulating hepatic insulin signalling[J]. Nat Commun, 2014, 5: 5684.
[20] Wang YZ, Lu J, Li YY, et al. MicroRNA-378b regulates ethanol-induced hepatic steatosis by targeting CaMKK2 to mediate lipid metabolism[J]. Bioengineered, 2021, 12(2): 12659-12676.
[21] 王霄霄,王海霞. 原发性高血压与代谢性疾病的相关性研究进展[J]. 中西医结合心脑血管病杂志, 2020,18(14):2262-2264.
[22] Mahmoud AM, Szczurek MR, Blackburn BK, et al. Hyperinsulinemia augments endothelin-1 protein expression and impairs vasodilation of human skeletal muscle arterioles[J]. Physiol Rep, 2016, 4(16):e12895.
[23] Sun YX, Wang J, Han B, et al. Elucidating the molecular mechanism of ischemic stroke using integrated analysis of miRNA, mRNA, and lncRNA expression profiles[J]. Front Integr Neurosci, 2021, 15: 638114.
[24] Huang SN, Zhang JH, Wan H, et al. Plasma extracellular vesicles microRNA-208b-3p and microRNA-143-3p as novel biomarkers for sudden cardiac death prediction in acute coronary syndrome[J]. Mol Omics, 2023, 19(3): 262-273.
[25] Wang KJ, Zhao X, Liu YZ, et al. Circulating miR-19b-3p, miR-134-5p and miR-186-5p are promising novel biomarkers for early diagnosis of acute myocardial infarction[J]. Cell Physiol Biochem, 2016, 38(3): 1015-1029.
[26] Liu W, Ling SK, Sun WJ, et al. Circulating microRNAs correlated with the level of coronary artery calcification in symptomatic patients[J]. Sci Rep, 2015, 5: 16099.
[27] Shin YK, Han AY, Hsieh YS, et al. Lancemaside A from Codonopsis lanceolata prevents hypertension by inhibiting NADPH oxidase 2-mediated MAPK signalling and improving NO bioavailability in rats[J]. J Pharm Pharmacol, 2019, 71(9): 1458-1468.
[28] Qi J, Li RJ, Fu LY, et al. Exercise training attenuates hypertension via suppressing ROS/MAPK/NF-κB/AT-1R pathway in the hypothalamic paraventricular nucleus[J]. Nutrients, 2022, 14(19):3968.
[29] 董凤梅,韩凌. 鬼针草总黄酮调控PI3K/Akt/mTOR自噬通路对高血压大鼠心肌纤维化的影响[J]. 广东医学, 2023,44(6): 720-728.
[30] Muthalif MM, Karzoun NA, Gaber L, et al. Angiotensin Ⅱ-induced hypertension: contribution of Ras GTPase/Mitogen-activated protein kinase and cytochrome P450 metabolites[J]. Hypertension, 2000, 36(4): 604-609.
[31] Benter IF, Francis I, Khan I, et al. Signal transduction involving Ras-GTPase contributes to development of hypertension and end-organ damage in spontaneously hypertensive rats-treated with L-NAME[J]. Pharmacol Res, 2005, 52(5): 401-412.
[32] Mehaffey E, Majid DSA. Tumor necrosis factor-α, kidney function, and hypertension[J]. Am J Physiol Renal Physiol, 2017,313(4):F1005-F1008.