年間 6 号発行
ISSN 印刷: 1040-8401
ISSN オンライン: 2162-6472
Indexed in
Diagnostic and Therapeutic Application of Exosomal microRNAs Inducing Inflammation in Type 2 Diabetes Mellitus
要約
Diabetes mellitus is a class of noncommunicable chronic metabolic disorders marked by hyperglycemia due to insulin production, insulin action or both and has reached epidemic levels around the world. The two most frequent types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Despite substantial improvements in the knowledge and treatment of DM, the associated incidence and mortality rates remain steadily increased. Reliable markers for the early detection, monitoring and focused treatment of DM are desperately required. Conversely, microRNAs (miRNAs) have received much significance due to their regulatory involvement in gene expression. Fascinatingly, exosomes can be enclosed into miRNAs to transport or distribute them into the target cells or tissues in which they have a physiological regulatory action. Thus, exosomal miRNAs are proving to be important regulators in the establishment and maintenance of DM, however, further mode of action will be needed to investigate in order to fully comprehend the pathophysiological process. Hereby, this review outlines the recent findings on the role of exosomal miRNAs intending to understand the precise function in diagnostic and therapeutic aspects in T2DM disease.
-
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(Suppl 1):S67-74.
-
Schmidt AM. Highlighting diabetes mellitus: The epidemic continues. Arterioscler Thromb Vasc Biol. 2018;38(1): e1-8.
-
Tiwari J, Gupta G, de Jesus Andreoli Pinto T, Sharma R, Pabreja K, Matta Y, Arora N, Mishra A, Sharma R, Dua K. Role of microRNAs (miRNAs) in the pathophysiology of diabetes mellitus. Panminerva Med. 2018;60(1):25-8.
-
Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185-200.
-
Castano C, Novials A, Parrizas M. Exosomes and diabetes. Diabetes Metab Res Rev. 2019;35(3):e3107.
-
Willms E, Cabanas C, Mager I, Wood MJA, Vader P. Extracellular vesicle heterogeneity: Subpopulations, isolation techniques, and diverse functions in cancer progression. Front Immunol. 2018;9:738.
-
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478): eaau6977.
-
Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells. 2019;8(4):307.
-
Pang H, Luo S, Xiao Y, Xia Y, Li X, Huang G, Xie Z, Zhou Z. Emerging Roles of Exosomes in T1DM. Front Immunol. 2020;11:593348.
-
Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev. 2015;87:3-14.
-
Lin J, Li J, Huang B, Liu J, Chen X, Chen XM, Xu YM, Huang LF, Wang XZ. Exosomes: Novel biomarkers for clinical diagnosis. Sci World J. 2015;2015:657086.
-
Lu Y, Liu D, Feng Q, Liu Z. Diabetic nephropathy: Perspective on extracellular vesicles. Front Immunol. 2020;11:943.
-
Preethi KA, Selvakumar SC, Ross K, Jayaraman S, Tusubira D, Sekar D. Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer. Mol Cancer. 2022;21(1):54.
-
Zhang J, Li S, Li L, Li M, Guo C, Yao J, Mi S. Exosome and exosomal microRNA: Trafficking, sorting, and function. Genom Proteom Bioinform. 2015;13(1):17-24.
-
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509-24.
-
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654-9.
-
Lebovitz HE. Insulin resistance: Definition and conse-quences. Exp Clin Endocrinol Diabetes. 2001;109(Suppl 2):S135-48.
-
Samuel VT, Shulman GI. Mechanisms for insulin resistance: Common threads and missing links. Cell. 2012;148(5):852-71.
-
Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, Winnay JN, Garcia-Martin R, Grinspoon SK, Gorden P, Kahn CR. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542(7642):450-5.
-
Su T, Xiao Y, Xiao Y, Guo Q, Li C, Huang Y, Deng Q, Wen J, Zhou F, Luo XH. Bone marrow mesenchymal stem cells-derived exosomal miR-29b-3p regulates aging-associated insulin resistance. ACS Nano. 2019;13(2):2450-62.
-
Liu T, Sun YC, Cheng P, Shao HG. Adipose tissue macro-phage-derived exosomal miR-29a regulates obesity-associated insulin resistance. Biochem Biophys Res Commun. 2019;515(2):352-8.
-
Li D, Song H, Shuo L, Wang L, Xie P, Li W, Liu J, Tong Y, Zhang CY, Jiang X, Li J, Zhang Y. Gonadal white adipose tissue-derived exosomal miR-222 promotes obesity-associated insulin resistance. Aging. 2020;12(22): 22719-43.
-
Ying W, Gao H, Dos Reis FCG, Bandyopadhyay G, Ofrecio JM, Luo Z, Ji Y, Jin Z, Ly C, Olefsky JM. miR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab. 2021;33(4):781-90.e5.
-
Li L, Zuo H, Huang X, Shen T, Tang W, Zhang X, An T, Dou L, Li J. Bone marrow macrophage-derived exosomal miR-143-5p contributes to insulin resistance in hepatocytes by repressing MKP5. Cell Prolif. 2021;54(12): e13140.
-
Byun JS, Lee HY, Tian J, Moon JS, Choi J, Lee SH, Kim YG, Yi HS. Effect of salivary exosomal miR-25-3p on periodontitis with insulin resistance. Front Immunol. 2022;12:775046.
-
Westermeier F, Riquelme JA, Pavez M, Garrido V, Diaz A, Verdejo HE, Castro PF, Garda L, Lavandero S. New molecular insights of insulin in diabetic cardiomyopathy. Front Physiol. 2016;7:125.
-
Wang X, Huang W, Liu G, Cai W, Millard RW, Wang Y, Chang J, Peng T, Fan GC. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol. 2014;74:139-50.
-
de Gonzalo-Calvo D, van der Meer RW, Rijzewijk LJ, Smit JW, Revuelta-Lopez E, Nasarre L, Escola-Gil JC, Lamb HJ, Llorente-Cortes V. Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes. Sci Rep. 2017;7(1):47.
-
Lu Y, Liu D, Feng Q, Liu Z. Diabetic nephropathy: Perspective on extracellular vesicles. Front Immunol. 2020;11:943.
-
Sun YM, Su Y, Li J, Wang LF. Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochem Biophys Res Commun. 2013;433(4):359-61.
-
Xie Y, Jia Y, Cuihua X, Hu F, Xue M, Xue Y. Urinary exosomal MicroRNA profiling in incipient type 2 diabetic kidney disease. J Diabetes Res. 2017;2017:6978984.
-
Li W, Yang S, Qiao R, Zhang J. Potential value of urinary exosome-derived let-7c-5p in the diagnosis and progression of type II diabetic nephropathy. Clin Lab. 2018;64(5):709-18.
-
Zang J, Maxwell AP, Simpson DA, McKay GJ. Differential expression of urinary exosomal microRNAs miR-21-5p and miR-30b-5p in individuals with diabetic kidney disease. Sci Rep. 2019;9(1):10900.
-
Zhao Y, Shen A, Guo F, Song Y, Jing N, Ding X, Pan M, Zhang H, Wang J, Wu L, Ma X, Feng L, Qin G. Urinary exosomal miRNA-4534 as a novel diagnostic bio-markerfor diabetic kidney disease. Front Endocrinol. 2020;11:590.
-
Liu D, Liu F, Li Z, Pan S, Xie J, Zhao Z, Liu Z, Zhang J, Liu Z. HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis. Cell Death Dis. 2021;12(3):255.
-
Cho NJ, Kim DY, Kwon SH, Ha TW, Kim HK, Lee MR, Chun SW, Park S, Lee EY, Gil HW. Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea. Kidney Res Clin Pract. 2021;40(3):383-91.
-
El Rami H, Barham R, Sun JK, Silva PS. Evidence-based treatment of diabetic retinopathy. Semin Ophthalmol. 2017;32(1):67-74.
-
Youngblood H, Robinson R, Sharma A, Sharma S. Proteomic biomarkers of retinal inflammation in diabetic retinopathy. Int J Mol Sci. 2019;20(19):4755.
-
Li W, Jin LY, Cui YB, Xie N. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1. Int Immunopharmacol. 2021;90:107010.
-
Jiang L, Cao H, Deng T, Yang M, Meng T, Yang H, Luo X. Serum exosomal miR-377-3p inhibits retinal pigment epithelium proliferation and offers a bio-marker for diabetic macular edema. J Int Med Res. 2021;49(4):3000605211002975.
-
Li W, Jin L, Cui Y, Nie A, Xie N, Liang G. Bone marrow mesenchymal stem cells-induced exosomal microR-NA-486-3p protects against diabetic retinopathy through TLR4/NF-KB axis repression. J Endocrinol Invest. 2021;44(6):1193-207.
-
Liu Y, Yang Q, Fu H, Wang J, Yuan S, Li X, Xie P, Hu Z, Liu Q. Muller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P1 in diabetic retinopathy. Mol Ther Nucleic Acids. 2021;27:491-504.
-
Liang G, Qin Z, Luo Y, Yin J, Shi Z, Wei R, Ma W. Exosomal microRNA-133b-3p from bone marrow mesenchymal stem cells inhibits angiogenesis and oxidative stress via FBN1 repression in diabetic retinopathy. Gene Ther. 2022;7:1-10.
-
Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, Bril V, Russell JW, Viswanathan V. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):42.
-
Javed S, Hayat T, Menon L, Alam U, Malik RA. Diabetic peripheral neuropathy in people with type 2 diabetes: Too little too late. Diabet Med. 2020;37(4):573-9.
-
Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285-93.
-
Fujita Y, Murakami T, Nakamura A. Recent advances in biomarkers and regenerative medicine for diabetic neuropathy. Int J Mol Sci. 2021;22(5):2301.
-
Venkat P, Cui C, Chopp M, Zacharek A, Wang F, Land-schoot-Ward J, Shen Y, Chen J. miR-126 mediates brain endothelial cell exosome treatment-induced neurorestorative effects after stroke in type 2 diabetes mellitus mice. Stroke. 2019;50(10):2865-74.
-
Wang L, Chopp M, Szalad A, Lu X, Zhang Y, Wang X, Cepparulo P, Lu M, Li C, Zhang ZG. Exosomes derived from Schwann cells ameliorate peripheral neuropathy in type 2 diabetic mice. Diabetes. 2020;69(4):749-59.
-
Fan B, Li C, Szalad A, Wang L, Pan W, Zhang R, Chopp M, Zhang ZG, Liu XS. Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia. 2020;63(2): 431-43.
-
Fan B, Chopp M, Zhang ZG, Liu XS. Treatment of diabetic peripheral neuropathy with engineered mesenchymal stromal cell-derived exosomes enriched with microRNA-146a provide amplified therapeutic efficacy. Exp Neurol. 2021;341:113694.
-
Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci. 2018;1411(1):153-65.
-
Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care. 2015;4(9):560-82.
-
Xiong Y, Chen L, Yan C, Zhou W, Endo Y, Liu J, Hu L, Hu Y, Mi B, Liu G. Circulating exosomal mir-20b-5p inhibition restores Wnt9b signaling and reverses diabetes-associated impaired wound healing. Small. 2020;16(3):e1904044.
-
Xiong Y, Chen L, Yu T, Yan C, Zhou W, Cao F, You X, Zhang Y, Sun Y, Liu J, Xue H, Hu Y, Chen D, Mi B, Liu G. Inhibition of circulating exosomal microRNA-15a-3p accelerates diabetic wound repair. Aging. 2020;12(10):8968-86.
-
Xu Y, Ouyang L, He L, Qu Y, Han Y, Duan D. Inhibition of exosomal miR-24-3p in diabetes restores angiogenesis and facilitates wound repair via targeting PIK3R3. J Cell Mol Med. 2020;24(23):13789-803.
-
Shi R, Jin Y, Hu W, Lian W, Cao C, Han S, Zhao S, Yuan H, Yang X, Shi J, Zhao H. Exosomes derived from mmu_circ_0000250-modified adipose-derived mesenchymal stem cells promote wound healing in diabetic mice by inducing miR-128-3p/SIRT1-mediated autophagy. Am J Physiol Cell Physiol. 2020;318(5):C848-56.
-
Huang C, Luo W, Wang Q, Ye Y, Fan J, Lin L, Shi C, Wei W, Chen H, Wu Y, Tang Y. Human mesenchymal stem cells promote ischemic repairment and angiogenesis of diabetic foot through exosome miRNA-21-5p. Stem Cell Res. 2021;52:102235.
-
Wang P, Theocharidis G, Vlachos IS, Kounas K, Lobao A, Shu B, Wu B, Xie J, Hu Z, Qi S, Tang B, Zhu J, Veves A. Exosomes derived from epidermal stem cells improve diabetic wound healing. J Invest Dermatol. 2022:S0022-202X(22)00119-1.
-
Yan C, Chen J, Wang C, Yuan M, Kang Y, Wu Z, Li W, Zhang G, Machens HG, Rinkevich Y, Chen Z, Yang X, Xu X. Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis. Drug Deliv. 2022;29(1):214-28.