Synergistic Treatment Approach for Pulmonary Fibrosis: Prednisone and Cyclophosphamide Regulation of Circular RNA MORF4L1 and MicroRNA-29a-3p Targeting BRD4
Abstract
This study aimed to explore the effect of prednisone (PDN) combined with cyclophosphamide (CTX) on bleomycin-induced pulmonary fibrosis (PF) in rats via circular RNA mortality factor 4 like 1 (MORF4L1)/microRNA (miR)-29a-3p/Bromodomain protein 4 (BRD4) axis.
A rat model of PF was induced by bleomycin and treated with PDN combined with CTX, and the lentiviral vectors that interfered with MORF4L1, miR-29a-3p, or BRD4 expression were injected into the tail vein at the same time. The mRNA expressions of MORF4L1, miR-29a-3p, BRD4, and fibrosis-associated proteins including fibronectin, connective tissue growth factor, and collagen I were detected by real-time quantitative polymerase chain reaction. The expression level of BRD4 protein in rat lungs was detected by Western blot analysis. Lung pathology of rats was observed by hematoxylin and eosin and Masson’s trichrome staining. Apoptosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The targeting relationship between miR-29a-3p and MORF4L1 or BRD4 was verified by the bioinformatics website and dual luciferase reporter experiment.
Bleomycin-induced PF enhanced MORF4L1 and BRD4 expression, inhibited miR-29a-3p expression, injured lung tissue, increased mRNA expression of fibrosis-related markers, and induced apoptosis in the lung tissue of rats. PDN combined with CTX had a therapeutic effect on PF in rats, which was further promoted by down-regulating MORF4L1 or up-regulating miR-29a-3p. After down-regulating miR-29a-3p or up-regulating BRD4, the effect of down-regulating MORF4L1 was reversed. MORF4L1 could bind to miR-29a-3p to target BRD4.
In short, PDN combined with CTX can effectively improve PF through downregulating MORF4L1 to enhance miR-29a-3p-targeted regulation of BRD4.
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2. Selman M, Pardo A, Kaminski N. Idiopathic pulmonary fibrosis: aberrant recapitulation of developmental programs? PLoS Med. 2008;5(3):e62.
3. Cao Z, Lis R, Ginsberg M, Chavez D, Shido K, Rabbany SY, et al. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. Nat Med. 2016;22(2):154-62.
4. Hofmann P, Sommer J, Theodorou K, Kirchhof L, Fischer A, Li Y, Perisic L, et al. Long non-coding RNA H19 regulates endothelial cell aging via inhibition of STAT3 signalling. Cardiovasc Res. 2019;115(1):230-42.
5. Inchingolo R, Varone F, Sgalla G, Richeldi L. Existing and emerging biomarkers for disease progression in idiopathic pulmonary fibrosis. Expert Rev Respir Med. 2019;13(1):39-51.
6. Liang H, Gu Y, Li T, Zhang Y, Huangfu L, Hu M, et al. Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis. Cell Death Dis. 2014;5(5):e1238.
7. Kulkarni T, O'Reilly P, Antony VB, Gaggar A, Thannickal VJ. Matrix Remodeling in Pulmonary Fibrosis and Emphysema. Am J Resp Cell Mol Biol. 2016;54(6):751-60.
8. Spagnolo P, Sverzellati N, Rossi G, Cavazza A, Tzouvelekis A, Crestani B, et al. Idiopathic pulmonary fibrosis: an update. Ann Med. 2015;47(1):15-27.
9. Chanda D, Otoupalova E, Smith SR, Volckaert T, De Langhe SP, Thannickal VJ. Developmental pathways in the pathogenesis of lung fibrosis. Mol Aspects Med. 2019;65(5):56-69.
10. Mora AL, Rojas M, Pardo A, Selman M. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease. Nature reviews. Drug Discovery. 2017;16(11):755-72.
11. Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J Clin Med. 2018;7(8).
12. Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, et al. Pirfenidone in idiopathic pulmonary fibrosis. Europ Rsp J. 2010;35(4):821-9.
14. Oku H, Shimizu T, Kawabata T, Nagira M, Hikita I, Ueyama A, et al. Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis. Eur J Pharmacol. 2008;590(1):400-8.
15. Fiorucci E, Lucantoni G, Paone G, Zotti M, Li BE, Serpilli M, et al. Colchicine, cyclophosphamide and prednisone in the treatment of mild-moderate idiopathic pulmonary fibrosis: comparison of three currently available therapeutic regimens. Eur Rev Med Pharmacol Sci. 2008;12(2):105-11.
16. Chen L. The biogenesis and emerging roles of circular RNAs. Nature reviews. Mol Cell Biol. 2016;17(4):205-11.
17. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333-8.
18. Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Comm. 2016;7(1):12429.
19. Hu W, Han Q, Zhao L, Wang L. Circular RNA circRNA_15698 aggravates the extracellular matrix of diabetic nephropathy mesangial cells via miR-185/TGF-β1. J Cell Physiol. 2019;34(2):1469-76.
20. Kristensen LS, Hansen TB, Venø MT, Kjems J. Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2018;37(5):555-65.
21. Hansen TB, Jensen TI, Clausen BH, Bramsen JB,
Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384-8.
22. Andrés-León E, Núñez-Torres R, Rojas AM. Rojas, miARma-Seq: a comprehensive tool for miRNA, mRNA and circRNA analysis. Sci Rep. 2016;6(5):25749.
23. Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget, 2017;8(42):73271-81.
24. Xiong DD, Dang YW, Lin P, Wen DY, He RQ, Luo DZ, et al. A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma. J Transl Med. 2018;16(1):220.
25. Zou C, Li J, Xiong S, Chen Y, Wu Q, Li X, Weathington NM, et al. Mortality factor 4 like 1 protein mediates epithelial cell death in a mouse model of pneumonia. Sci Transl Med. 2015;7(311):311ra171.
26. Wu Q, Han L, Gui W, Wang F, Yan W, Jiang H. MiR-503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica-induced pulmonary fibrosis. J Cell Mol Med. 2020;24(24):14339-48.
27. Zhang J. The effects of miR-27a-3p-mediated Smurf2 on bleomycin A5-induced pulmonary fibrosis in rats. Cell Mol Biol. 2020;66(3):79-84.
28. Bai J, Deng J, Han Z, Cui Y, He R, Gu Y, Zhang Q. CircRNA_0026344 via exosomal miR-21 regulation of Smad7 is involved in aberrant cross-talk of epithelium-fibroblasts during cigarette smoke-induced pulmonary fibrosis. Toxicol Lett. 2021;347(12):58-66.
29. Cushing L. miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol. 2011;45(2):287-94.
30. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A. 2008;105(35):13027-32.
31. Luo Y, Dong HY, Zhang B, Feng Z, Liu Y, Gao YQ, et al. miR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation. Hypertension. 2015;65(2):414-20.
32. Li P, Hao X, Liu J, Zhang Q, Liang Z, Li X, et al. miR-29a-3p Regulates Autophagy by Targeting Akt3-Mediated mTOR in SiO2-Induced Lung Fibrosis. Int J Mol Sci. 2023;24(14):11440.
33. Tang X, Peng R, Phillips JE, Deguzman J, Ren Y, Apparsundaram S, et al. Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis. Am J Pathol. 2013;183(2):470-9.
34. Sanders YY, Lyv X, Zhou QJ, Xiang Z, Stanford D, Bodduluri S, et al. Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice. JCI insight. 2020;5(14).
35. Chen Y, Zhang Q, Zhou Y, Yang Z, Tan M. Inhibition of miR-182-5p attenuates pulmonary fibrosis via TGF-β/Smad pathway. Hum Exp Toxicol. 2020;39(5):683-95.
36. Wang Y., et al., Hepatic NPC1L1 overexpression attenuates alcoholic autophagy in mice. Mol Med Rep. 2019;20(4):3224-32.
37. Zhou J. Effect of fecal microbiota transplantation on experimental colitis in mice. Exp Ther Med. 2019;17(4):2581-6.
38. Aso S. Systemic glucocorticoids plus cyclophosphamide for acute exacerbation of idiopathic pulmonary fibrosis: a retrospective nationwide study. Sarcoidosis Vasc Diffuse Lung Dis. 2019;36(2):116-23.
39. Naccache JM, Montil M, Cadranel J, Cachanado M, Cottin V, Crestani B, et al. Study protocol: exploring the efficacy of cyclophosphamide added to corticosteroids for treating acute exacerbation of idiopathic pulmonary fibrosis; a randomized double-blind, placebo-controlled, multi-center phase III trial (EXAFIP). BMC pulmonary medicine, 2019;19(1):75-9.
40. Hozumi, H. Efficacy of corticosteroid and intravenous cyclophosphamide in acute exacerbation of idiopathic pulmonary fibrosis: A propensity score-matched analysis. Respirology. 2019;24(8):792-8.
41. Yu W, Guo F, Song X. Song, Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models. Pharm Biol. 2017;55(1):450-5.
42. Gothe F, Schmautz A, Häusler K, Tran NB, Kappler M, Griese M. Treating Allergic Bronchopulmonary Aspergillosis with Short-Term Prednisone and Itraconazole in Cystic Fibrosis. J Allergy Clin Immunol Pract. 2020;8(8):2608-2614.e3.
43. Zhang H. Prednisone Ameliorates Atrial Inflammation and Fibrosis in Atrial Tachypacing Dogs. Int Heart J. 2022;63(2):347-55.
44. Gao H. Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis [published correction appears in Ann Rheum Dis. Ann Rheum Dis. 2023;82(5):688-97.
45. Ahlmann M, Hempel G. The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. Cancer Chemother Pharmacol. 2016;78(4):661-71.
46. Teles KA, Medeiros-Souza P, Lima FAC, Araújo BG, Lima RAC. Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review. Rev Bras Reumatol Engl Ed. 2017;57(6):596-604.
47. Liu H, Wang X, Wang ZY, Li L. Circ_0080425 inhibits cell proliferation and fibrosis in diabetic nephropathy via sponging miR-24-3p and targeting fibroblast growth factor 11. J Cell Physiol. 2020,235(5):4520-9.
48. Li G, Qin Y, Qin S, Zhou X, Zhao W, Zhang D. Circ_WBSCR17 aggravates inflammatory responses and fibrosis by targeting miR-185-5p/SOX6 regulatory axis in high glucose-induced human kidney tubular cells. Life Sci. 2020;259(14):18269.
49. Li S, Song F, Lei X, Li J, Li F, Tan H. hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis. Aging. 2020;12(12):11517-29.
50. Ji D, Chen GF, Wang JC, Ji SH, Wu XW, Lu XJ, et al. Hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3. Aging, 2020;12(2):1643-55.
51. Wang W, Feng J, Zhou H, Li Q. Circ_0123996 promotes cell proliferation and fibrosisin mouse mesangial cells through sponging miR-149-5p and inducing Bach1 expression. Gene. 2020;761(5):144971.
53. Ai K, Zhu X, Kang Y, Li H, Zhang L. miR-130a-3p inhibition protects against renal fibrosis in vitro via the TGF-β1/Smad pathway by targeting SnoN. Exp Mol Pathol. 2020;112(23):104358.
54. Cheng L, Tu C, Min Y, He D, Wan S, Xiong F. MiR-194 targets Runx1/Akt pathway to reduce renal fibrosis in mice with unilateral ureteral obstruction. Int Urol Nephrol. 2020;52(9):1801-8.
55. Xue Y, Fan X, Yang R, Jiao Y, Li Y. miR-29b-3p inhibits post-infarct cardiac fibrosis by targeting FOS. Biosci Rep. 2020;40(9).
2. Selman M, Pardo A, Kaminski N. Idiopathic pulmonary fibrosis: aberrant recapitulation of developmental programs? PLoS Med. 2008;5(3):e62.
3. Cao Z, Lis R, Ginsberg M, Chavez D, Shido K, Rabbany SY, et al. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. Nat Med. 2016;22(2):154-62.
4. Hofmann P, Sommer J, Theodorou K, Kirchhof L, Fischer A, Li Y, Perisic L, et al. Long non-coding RNA H19 regulates endothelial cell aging via inhibition of STAT3 signalling. Cardiovasc Res. 2019;115(1):230-42.
5. Inchingolo R, Varone F, Sgalla G, Richeldi L. Existing and emerging biomarkers for disease progression in idiopathic pulmonary fibrosis. Expert Rev Respir Med. 2019;13(1):39-51.
6. Liang H, Gu Y, Li T, Zhang Y, Huangfu L, Hu M, et al. Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis. Cell Death Dis. 2014;5(5):e1238.
7. Kulkarni T, O'Reilly P, Antony VB, Gaggar A, Thannickal VJ. Matrix Remodeling in Pulmonary Fibrosis and Emphysema. Am J Resp Cell Mol Biol. 2016;54(6):751-60.
8. Spagnolo P, Sverzellati N, Rossi G, Cavazza A, Tzouvelekis A, Crestani B, et al. Idiopathic pulmonary fibrosis: an update. Ann Med. 2015;47(1):15-27.
9. Chanda D, Otoupalova E, Smith SR, Volckaert T, De Langhe SP, Thannickal VJ. Developmental pathways in the pathogenesis of lung fibrosis. Mol Aspects Med. 2019;65(5):56-69.
10. Mora AL, Rojas M, Pardo A, Selman M. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease. Nature reviews. Drug Discovery. 2017;16(11):755-72.
11. Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J Clin Med. 2018;7(8).
12. Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, et al. Pirfenidone in idiopathic pulmonary fibrosis. Europ Rsp J. 2010;35(4):821-9.
14. Oku H, Shimizu T, Kawabata T, Nagira M, Hikita I, Ueyama A, et al. Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis. Eur J Pharmacol. 2008;590(1):400-8.
15. Fiorucci E, Lucantoni G, Paone G, Zotti M, Li BE, Serpilli M, et al. Colchicine, cyclophosphamide and prednisone in the treatment of mild-moderate idiopathic pulmonary fibrosis: comparison of three currently available therapeutic regimens. Eur Rev Med Pharmacol Sci. 2008;12(2):105-11.
16. Chen L. The biogenesis and emerging roles of circular RNAs. Nature reviews. Mol Cell Biol. 2016;17(4):205-11.
17. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333-8.
18. Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Comm. 2016;7(1):12429.
19. Hu W, Han Q, Zhao L, Wang L. Circular RNA circRNA_15698 aggravates the extracellular matrix of diabetic nephropathy mesangial cells via miR-185/TGF-β1. J Cell Physiol. 2019;34(2):1469-76.
20. Kristensen LS, Hansen TB, Venø MT, Kjems J. Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2018;37(5):555-65.
21. Hansen TB, Jensen TI, Clausen BH, Bramsen JB,
Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384-8.
22. Andrés-León E, Núñez-Torres R, Rojas AM. Rojas, miARma-Seq: a comprehensive tool for miRNA, mRNA and circRNA analysis. Sci Rep. 2016;6(5):25749.
23. Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget, 2017;8(42):73271-81.
24. Xiong DD, Dang YW, Lin P, Wen DY, He RQ, Luo DZ, et al. A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma. J Transl Med. 2018;16(1):220.
25. Zou C, Li J, Xiong S, Chen Y, Wu Q, Li X, Weathington NM, et al. Mortality factor 4 like 1 protein mediates epithelial cell death in a mouse model of pneumonia. Sci Transl Med. 2015;7(311):311ra171.
26. Wu Q, Han L, Gui W, Wang F, Yan W, Jiang H. MiR-503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica-induced pulmonary fibrosis. J Cell Mol Med. 2020;24(24):14339-48.
27. Zhang J. The effects of miR-27a-3p-mediated Smurf2 on bleomycin A5-induced pulmonary fibrosis in rats. Cell Mol Biol. 2020;66(3):79-84.
28. Bai J, Deng J, Han Z, Cui Y, He R, Gu Y, Zhang Q. CircRNA_0026344 via exosomal miR-21 regulation of Smad7 is involved in aberrant cross-talk of epithelium-fibroblasts during cigarette smoke-induced pulmonary fibrosis. Toxicol Lett. 2021;347(12):58-66.
29. Cushing L. miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol. 2011;45(2):287-94.
30. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A. 2008;105(35):13027-32.
31. Luo Y, Dong HY, Zhang B, Feng Z, Liu Y, Gao YQ, et al. miR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation. Hypertension. 2015;65(2):414-20.
32. Li P, Hao X, Liu J, Zhang Q, Liang Z, Li X, et al. miR-29a-3p Regulates Autophagy by Targeting Akt3-Mediated mTOR in SiO2-Induced Lung Fibrosis. Int J Mol Sci. 2023;24(14):11440.
33. Tang X, Peng R, Phillips JE, Deguzman J, Ren Y, Apparsundaram S, et al. Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis. Am J Pathol. 2013;183(2):470-9.
34. Sanders YY, Lyv X, Zhou QJ, Xiang Z, Stanford D, Bodduluri S, et al. Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice. JCI insight. 2020;5(14).
35. Chen Y, Zhang Q, Zhou Y, Yang Z, Tan M. Inhibition of miR-182-5p attenuates pulmonary fibrosis via TGF-β/Smad pathway. Hum Exp Toxicol. 2020;39(5):683-95.
36. Wang Y., et al., Hepatic NPC1L1 overexpression attenuates alcoholic autophagy in mice. Mol Med Rep. 2019;20(4):3224-32.
37. Zhou J. Effect of fecal microbiota transplantation on experimental colitis in mice. Exp Ther Med. 2019;17(4):2581-6.
38. Aso S. Systemic glucocorticoids plus cyclophosphamide for acute exacerbation of idiopathic pulmonary fibrosis: a retrospective nationwide study. Sarcoidosis Vasc Diffuse Lung Dis. 2019;36(2):116-23.
39. Naccache JM, Montil M, Cadranel J, Cachanado M, Cottin V, Crestani B, et al. Study protocol: exploring the efficacy of cyclophosphamide added to corticosteroids for treating acute exacerbation of idiopathic pulmonary fibrosis; a randomized double-blind, placebo-controlled, multi-center phase III trial (EXAFIP). BMC pulmonary medicine, 2019;19(1):75-9.
40. Hozumi, H. Efficacy of corticosteroid and intravenous cyclophosphamide in acute exacerbation of idiopathic pulmonary fibrosis: A propensity score-matched analysis. Respirology. 2019;24(8):792-8.
41. Yu W, Guo F, Song X. Song, Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models. Pharm Biol. 2017;55(1):450-5.
42. Gothe F, Schmautz A, Häusler K, Tran NB, Kappler M, Griese M. Treating Allergic Bronchopulmonary Aspergillosis with Short-Term Prednisone and Itraconazole in Cystic Fibrosis. J Allergy Clin Immunol Pract. 2020;8(8):2608-2614.e3.
43. Zhang H. Prednisone Ameliorates Atrial Inflammation and Fibrosis in Atrial Tachypacing Dogs. Int Heart J. 2022;63(2):347-55.
44. Gao H. Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis [published correction appears in Ann Rheum Dis. Ann Rheum Dis. 2023;82(5):688-97.
45. Ahlmann M, Hempel G. The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. Cancer Chemother Pharmacol. 2016;78(4):661-71.
46. Teles KA, Medeiros-Souza P, Lima FAC, Araújo BG, Lima RAC. Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review. Rev Bras Reumatol Engl Ed. 2017;57(6):596-604.
47. Liu H, Wang X, Wang ZY, Li L. Circ_0080425 inhibits cell proliferation and fibrosis in diabetic nephropathy via sponging miR-24-3p and targeting fibroblast growth factor 11. J Cell Physiol. 2020,235(5):4520-9.
48. Li G, Qin Y, Qin S, Zhou X, Zhao W, Zhang D. Circ_WBSCR17 aggravates inflammatory responses and fibrosis by targeting miR-185-5p/SOX6 regulatory axis in high glucose-induced human kidney tubular cells. Life Sci. 2020;259(14):18269.
49. Li S, Song F, Lei X, Li J, Li F, Tan H. hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis. Aging. 2020;12(12):11517-29.
50. Ji D, Chen GF, Wang JC, Ji SH, Wu XW, Lu XJ, et al. Hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3. Aging, 2020;12(2):1643-55.
51. Wang W, Feng J, Zhou H, Li Q. Circ_0123996 promotes cell proliferation and fibrosisin mouse mesangial cells through sponging miR-149-5p and inducing Bach1 expression. Gene. 2020;761(5):144971.
53. Ai K, Zhu X, Kang Y, Li H, Zhang L. miR-130a-3p inhibition protects against renal fibrosis in vitro via the TGF-β1/Smad pathway by targeting SnoN. Exp Mol Pathol. 2020;112(23):104358.
54. Cheng L, Tu C, Min Y, He D, Wan S, Xiong F. MiR-194 targets Runx1/Akt pathway to reduce renal fibrosis in mice with unilateral ureteral obstruction. Int Urol Nephrol. 2020;52(9):1801-8.
55. Xue Y, Fan X, Yang R, Jiao Y, Li Y. miR-29b-3p inhibits post-infarct cardiac fibrosis by targeting FOS. Biosci Rep. 2020;40(9).
| Files | ||
| Issue | Vol 23 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i4.16217 | |
| Keywords | ||
| Bromodomain protein 4 Circular RNA mortality factor 4 like 1 Cyclophosphamide MicroRNA-29a-3p Prednisone Pulmonary fibrosis | ||
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How to Cite
1.
Wang D, Zhao H, Li B, Quan F. Synergistic Treatment Approach for Pulmonary Fibrosis: Prednisone and Cyclophosphamide Regulation of Circular RNA MORF4L1 and MicroRNA-29a-3p Targeting BRD4. Iran J Allergy Asthma Immunol. 2024;23(4):437-451.
