Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Study of MicroRNA-124 in Patients with Lupus Nephritis

Author(s): Mostafa Abdelsalam*, Maysaa El Sayed Zaki, Nermin Youssef Abo El-Kheir, Mona Foda Salama and Asmaa Osama Bakr Seddik Osman

Volume 24, Issue 10, 2024

Published on: 15 January, 2024

Page: [1180 - 1185] Pages: 6

DOI: 10.2174/0118715303250919231010073608

Price: $65

Abstract

Background: Lupus nephritis is associated with a six-fold increase in mortality compared with the general population. MicroRNAs studies revealed that increased MicroRNA -21 and MicroRNA -155 levels represent risk factors for active LN patients. MicroRNAs can be used as biomarkers in the diagnosis of clinical stages of LN.

Objectives: The present study aimed to determine the level of miR-124 in patients with lupus nephritis by reverse transcriptase real-time polymerase chain reaction compared to healthy control and correlate its levels with biochemical findings in those patients.

Methods: The study was a case-control study that included fifty patients with lupus nephritis in addition to fifty healthy controls. Blood samples from the participants were subjected to the determination of serological markers of SLE. Moreover, real-time PCR was used for the determination of miR-124.

Results: The comparison of Micro-RNA124 between patients and control subjects revealed a statistically significant decrease in Micro-RNA124 in patients (1.193 ± 0.56) compared to the control (3.36 ± 0.50, p <0.001); the comparison of the level of MicroRNA 124 in the patients with different clinical and serological findings of SLE revealed a significant decrease in the level of MicroRNA 124 in patients with muscular findings (1.02 ± 0.5) compared to the patients with negative manifestations (1.47 ± 0.5, p =0.005).

Conclusion: In the present study, a comparison of MicroRNA-124 in LN patients with different stages compared to normal control showed a statistically significant decrease in Micro-RNA124 in patients with lupus nephritis p <0.001 with significant correlation to the patients’ different clinical and serological findings of SLE. Therefore, it may be used as a new noninvasive therapeutic approach to monitor response to therapy, predict relapses, and identify the degree of the activity of the disease or the progression to the chronic stage.

Graphical Abstract

[1]
Moroni, G. Severe lupus nephritis in the present days. Nephrol. Front. Nephrol., 2022, 22, 1-8.
[2]
Tektonidou, M.G.; Dasgupta, A.; Ward, M.M. Risk of end-stage renal disease in patients with lupus nephritis, 1971-2015: A systematic review and Bayesian meta-analysis. Arthritis Rheumatol., 2016, 68(6), 1432-1441.
[http://dx.doi.org/10.1002/art.39594] [PMID: 26815601]
[3]
Moroni, G.; Vercelloni, P.G.; Quaglini, S.; Gatto, M.; Gianfreda, D.; Sacchi, L.; Raffiotta, F.; Zen, M.; Costantini, G.; Urban, M.L.; Pieruzzi, F.; Messa, P.; Vaglio, A.; Sinico, R.A.; Doria, A. Changing patterns in clinical–histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis. Ann. Rheum. Dis., 2018, 77(9), 1318-1325.
[http://dx.doi.org/10.1136/annrheumdis-2017-212732] [PMID: 29730634]
[4]
Hanly, J.G.; O’Keeffe, A.G.; Su, L.; Urowitz, M.B.; Romero-Diaz, J.; Gordon, C.; Bae, S.C.; Bernatsky, S.; Clarke, A.E.; Wallace, D.J.; Merrill, J.T.; Isenberg, D.A.; Rahman, A.; Ginzler, E.M.; Fortin, P.; Gladman, D.D.; Sanchez-Guerrero, J.; Petri, M.; Bruce, I.N.; Dooley, M.A.; Ramsey-Goldman, R.; Aranow, C.; Alarcón, G.S.; Fessler, B.J.; Steinsson, K.; Nived, O.; Sturfelt, G.K.; Manzi, S.; Khamashta, M.A.; van Vollenhoven, R.F.; Zoma, A.A.; Ramos-Casals, M.; Ruiz-Irastorza, G.; Lim, S.S.; Stoll, T.; Inanc, M.; Kalunian, K.C.; Kamen, D.L.; Maddison, P.; Peschken, C.A.; Jacobsen, S.; Askanase, A.; Theriault, C.; Thompson, K.; Farewell, V. The frequency and outcome of lupus nephritis: Results from an international inception cohort study. Rheumatology, 2016, 55(2), 252-262.
[http://dx.doi.org/10.1093/rheumatology/kev311] [PMID: 26342222]
[5]
Yap, D.Y.H.; Tang, C.S.O.; Ma, M.K.M.; Lam, M.F.; Chan, T.M. Survival analysis and causes of mortality in patients with lupus nephritis. Nephrol. Dial. Transplant., 2012, 27(8), 3248-3254.
[http://dx.doi.org/10.1093/ndt/gfs073] [PMID: 22523116]
[6]
Fanouriakis, A.; Kostopoulou, M.; Cheema, K.; Anders, H.J.; Aringer, M.; Bajema, I.; Boletis, J.; Frangou, E.; Houssiau, F.A.; Hollis, J.; Karras, A.; Marchiori, F.; Marks, S.D.; Moroni, G.; Mosca, M.; Parodis, I.; Praga, M.; Schneider, M.; Smolen, J.S.; Tesar, V.; Trachana, M.; van Vollenhoven, R.F.; Voskuyl, A.E.; Teng, Y.K.O.; van Leew, B.; Bertsias, G.; Jayne, D.; Boumpas, D.T. 2019 Update of the joint european league against rheumatism and european renal association–european dialysis and transplant association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis. Ann. Rheum. Dis., 2020, 79(6), 713-723.
[http://dx.doi.org/10.1136/annrheumdis-2020-216924] [PMID: 32220834]
[7]
Weening, J.J.; D’agati, V.D.; Schwartz, M.M.; Seshan, S.V.; Alpers, C.E.; Appel, G.B.; Balow, J.E.; Bruijn, J.A.N.A.; Cook, T.; Ferrario, F.; Fogo, A.B.; Ginzler, E.M.; Hebert, L.E.E.; Hill, G.; Hill, P.; Jennette, J.C.; Kong, N.C.; Lesavre, P.; Lockshin, M.; Looi, L.M.; Makino, H.; Moura, L.A.; Nagata, M. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int., 2004, 65(2), 521-530.
[http://dx.doi.org/10.1111/j.1523-1755.2004.00443.x] [PMID: 14717922]
[8]
Khoshmirsafa, M.; Kianmehr, N.; Falak, R.; Mowla, S.J.; Seif, F.; Mirzaei, B.; Valizadeh, M.; Shekarabi, M. Elevated expression of miR‐21 and miR‐155 in peripheral blood mononuclear cells as potential biomarkers for lupus nephritis. Int. J. Rheum. Dis., 2019, 22(3), 458-467.
[http://dx.doi.org/10.1111/1756-185X.13410] [PMID: 30398001]
[9]
So, B.Y.F.; Yap, D.Y.H.; Chan, T.M. MicroRNAs in lupus nephritis–role in disease pathogenesis and clinical applications. Int. J. Mol. Sci., 2021, 22(19), 10737.
[http://dx.doi.org/10.3390/ijms221910737] [PMID: 34639078]
[10]
Hedrich, C.M. Epigenetics in SLE. Curr. Rheumatol. Rep., 2017, 19(9), 58.
[http://dx.doi.org/10.1007/s11926-017-0685-1] [PMID: 28752494]
[11]
Dziedziejko, V.; Taheri, M. Exploring the role of non-coding rnas in the pathophysiology of systemic lupus erythematosus. Int. J. Mol. Sci., 2020, 10, 5050.
[12]
Tsai, C.Y.; Shen, C.Y.; Liu, C.W.; Hsieh, S.C.; Liao, H.T.; Li, K.J.; Lu, C.S.; Lee, H.T.; Lin, C.S.; Wu, C.H.; Kuo, Y.M.; Yu, C.L. Aberrant non-coding RNA expression in patients with systemic lupus erythematosus: Consequences for immune dysfunctions and tissue damage. Biomolecules, 2020, 10(12), 1641.
[http://dx.doi.org/10.3390/biom10121641] [PMID: 33291347]
[13]
Honarpisheh, M.; Köhler, P.; von Rauchhaupt, E.; Lech, M. The involvement of microRNAs in modulation of innate and adaptive immunity in systemic lupus erythematosus and lupus Nephritis. J. Immunol. Res., 2018, 2018, 1-15.
[http://dx.doi.org/10.1155/2018/4126106] [PMID: 29854836]
[14]
Chafin, C.B.; Reilly, C.M. MicroRNAs implicated in the immunopathogenesis of lupus nephritis. Clin. Dev. Immunol., 2013, 2013, 1-13.
[http://dx.doi.org/10.1155/2013/430239] [PMID: 23983769]
[15]
Esteller, M. Non-coding RNAs in human disease. Nat. Rev. Genet., 2011, 12(12), 861-874.
[http://dx.doi.org/10.1038/nrg3074] [PMID: 22094949]
[16]
Fabian, M.R.; Sonenberg, N.; Filipowicz, W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem., 2010, 79(1), 351-379.
[http://dx.doi.org/10.1146/annurev-biochem-060308-103103] [PMID: 20533884]
[17]
Wilczynska, A.; Bushell, M. The complexity of miRNA-mediated repression. Cell Death Differ., 2015, 22(1), 22-33.
[http://dx.doi.org/10.1038/cdd.2014.112] [PMID: 25190144]
[18]
Zhang, L.; Zhang, X.; Si, F. MicroRNA-124 represents a novel diagnostic marker in human lupus nephritis and plays an inhibitory effect on the growth and inflammation of renal mesangial cells by targeting TRAF6. Int. J. Clin. Exp. Pathol., 2019, 12(5), 1578-1588.
[19]
Tangtanatakul, P.; Klinchanhom, S.; Sodsai, P.; Sutichet, T.; Promjeen, C.; Avihingsanon, Y.; Hirankarn, N. Down-regulation of let-7a and miR-21 in urine exosomes from lupus nephritis patients during disease flare. Am. J. Transl. Res., 2017, 9, 3796-3803.
[20]
Wang, W.; Gao, J.; Wang, F. MiR-663a/MiR-423-5p are involved in the pathogenesis of lupus nephritis via modulating the activation of NF-kappaB by targeting TNIP2. Am. J. Transl. Res., 2017, 9, 3796-3803.
[21]
Qin, Z.; Wang, P.Y.; Su, D.F.; Liu, X. miRNA-124 in immune system and immune disorders. Front. Immunol., 2016, 7, 406.
[http://dx.doi.org/10.3389/fimmu.2016.00406] [PMID: 27757114]
[22]
Sun, Y.; Li, Q.; Gui, H.; Xu, D.P.; Yang, Y.L.; Su, D.F.; Liu, X. MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines. Cell Res., 2013, 23(11), 1270-1283.
[http://dx.doi.org/10.1038/cr.2013.116] [PMID: 23979021]
[23]
Portillo, J.A.C.; Greene, J.A.; Schwartz, I.; Subauste, M.C.; Subauste, C.S. Blockade of CD40-TRAF2,3 or CD40-TRAF6 is sufficient to inhibit pro-inflammatory responses in non-haematopoietic cells. Immunology, 2015, 144(1), 21-33.
[http://dx.doi.org/10.1111/imm.12361] [PMID: 25051892]
[24]
Petri, M.; Orbai, A.M.; Alarcón, G.S.; Gordon, C.; Merrill, J.T.; Fortin, P.R.; Bruce, I.N.; Isenberg, D.; Wallace, D.J.; Nived, O.; Sturfelt, G.; Ramsey-Goldman, R.; Bae, S.C.; Hanly, J.G.; Sánchez-Guerrero, J.; Clarke, A.; Aranow, C.; Manzi, S.; Urowitz, M.; Gladman, D.; Kalunian, K.; Costner, M.; Werth, V.P.; Zoma, A.; Bernatsky, S.; Ruiz-Irastorza, G.; Khamashta, M.A.; Jacobsen, S.; Buyon, J.P.; Maddison, P.; Dooley, M.A.; van Vollenhoven, R.F.; Ginzler, E.; Stoll, T.; Peschken, C.; Jorizzo, J.L.; Callen, J.P.; Lim, S.S.; Fessler, B.J.; Inanc, M.; Kamen, D.L.; Rahman, A.; Steinsson, K.; Franks, A.G., Jr; Sigler, L.; Hameed, S.; Fang, H.; Pham, N.; Brey, R.; Weisman, M.H.; McGwin, G., Jr; Magder, L.S. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum., 2012, 64(8), 2677-2686.
[http://dx.doi.org/10.1002/art.34473] [PMID: 22553077]
[25]
Jiang, S.; Li, C.; McRae, G.; Lykken, E.; Sevilla, J.; Liu, S.Q.; Wan, Y.; Li, Q.J. MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5. Sci. Signal., 2014, 7(316), ra25.
[http://dx.doi.org/10.1126/scisignal.2004824] [PMID: 24619648]
[26]
Ma, C.; Li, Y.; Li, M.; Deng, G.; Wu, X.; Zeng, J.; Hao, X.; Wang, X.; Liu, J.; Cho, W.C.S.; Liu, X.; Wang, Y. microRNA-124 negatively regulates TLR signaling in alveolar macrophages in response to mycobacterial infection. Mol. Immunol., 2014, 62(1), 150-158.
[http://dx.doi.org/10.1016/j.molimm.2014.06.014] [PMID: 24995397]
[27]
Koukos, G.; Polytarchou, C.; Kaplan, J.L.; Morley-Fletcher, A.; Gras-Miralles, B.; Kokkotou, E.; Baril-Dore, M.; Pothoulakis, C.; Winter, H.S.; Ili-opoulos, D. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tis-sues of pediatric patients with ulcerative coli-tis. Gastroenterology, 2013, 145, 842-852.
[28]
Zhou, Q.; Long, L.; Shi, G.; Zhang, J.; Wu, T.; Zhou, B. Research of the methylation status of miR-124a gene promoter among rheumatoid arthritis patients. Clin. Dev. Immunol., 2013, 2013, 1-4.
[http://dx.doi.org/10.1155/2013/524204] [PMID: 24223605]
[29]
Cristian, C. Urinary biomarkers in lupus nephritis. J. Transl., 2020, 3, 100042.
[30]
Chen, J.; Peng, L.; Zhao, Z.; Yang, Q.; Yin, F.; Liu, M.; Luo, X.; He, C.; He, Y. HDAC1 potentiates CD4 + T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus. Cell. Immunol., 2021, 362, 104284.
[http://dx.doi.org/10.1016/j.cellimm.2021.104284] [PMID: 33550188]
[31]
Feng, L.L.; Xin, W.N.; Tian, X.L. MALAT1 modulates miR-146’s protection of microvascular endothelial cells against LPS-induced NF-κB activation and inflammatory injury. Innate Immun., 2019, 25(7), 433-443.
[http://dx.doi.org/10.1177/1753425919861427] [PMID: 31291804]
[32]
Shao, B.Y.; Zhang, S.F.; Li, H.D.; Meng, X.M.; Chen, H.Y. Epigenetics and inflammation in diabetic nephropathy. Front. Physiol., 2021, 12, 649587.
[33]
Sjöwall, C.; Zickert, A.; Skogh, T.; Wetterö, J.; Gunnarsson, I. Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis. Arthritis Research &. Therapy, 2009, 11(6), R188.
[34]
Narayanan, K.; Marwaha, V.; Shanmuganandan, K.; Shankar, S. Correlation between systemic lupus erythematosus disease activity index, C3, C4 and anti-dsDNA antibodies. Med. J. Armed Forces India, 2010, 66(2), 102-107.
[http://dx.doi.org/10.1016/S0377-1237(10)80118-2] [PMID: 27365721]
[35]
Hassani, M.; Dehani, M.; Zare Rafie, M.; Esmaeilzadeh, E.; Davar, S.; Pakzad, B.; Mosallaei, M.; Hoseini, S.M.; Bayat, H.; Soosanabadi, M. Investigation of rs531564 polymorphism in the primary MicroRNA-124 gene in patients with systemic lupus erythematosus and rheumatoid arthritis: Association with disease susceptibility and clinical characteristics. Iran. J. Allergy Asthma Immunol., 2021, 20(3), 303-313.
[http://dx.doi.org/10.18502/ijaai.v20i3.6336] [PMID: 34134452]
[36]
Mashaly, M.E.S.; Alkasaby, N.M.; Bakr, A. Viral pathogens of acute gastroenteritis in Egyptian children: role of the parechovirus. BMC Infect. Dis., 2022, 22(1), 584.
[http://dx.doi.org/10.1186/s12879-022-07562-5]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy