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The effects of miR-27a-3p-mediated Smurf2 on bleomycin A5-induced pulmonary fibrosis in rats
Corresponding Author(s) : Qin Zhang
Cellular and Molecular Biology,
Vol. 66 No. 3: Issue 3
Abstract
This study aimed to explore the effects of miR-27a-3p-mediated Smurf2 on bleomycin A5-induced pulmonary fibrosis in rats. Sixty clean-grade SD rats were made into models of pulmonary fibrosis induced by bleomycin A5. They were randomly divided into the control group (fed as usual), the bleomycin A5 group, and the miR-27a-3p group according to the modeling. Pathological sections and morphological observations were performed on the lung tissues of all rats, and the expression of miR-27a-3p, Smurf2 mRNA, Smurf2 protein, collagen type I (Col I), collagen type III (Col III), and related inflammatory factors in lung tissues were measured. Dual fluorescein detection was performed for miR-27a-3p and Smurf2 in lung tissues. The lung tissue of rats in the bleomycin A5 group showed obvious pathological changes. The degree of pulmonary fibrosis in the miR-27a-3p group was significantly lower than that in the bleomycin A5 group. The expression levels of Smurf2 mRNA, Smurf2 protein, Col I, Col III, and related inflammatory factors in the lung tissue of rats in the control group were notably lower than rats in the bleomycin A5 group and the miR-27a-3p group (levels of those factors in the miR-27a-3p group were lower than the bleomycin A5 group). The expression level of miR-27a-3p in the lung tissue of rats in the control group was significantly higher than that in the bleomycin A5 group and the miR-27a-3p group (miR-27a-3p level in the miR-27a-3p group was significantly higher than in the bleomycin A5 group). Results of dual fluorescein detection demonstrated that Smurf2 was a direct target gene of miR-27a-3p, and the expression of miR-27a-3p negatively associated with Smurf2. Up-regulation of miR-27a-3p expression can effectively improve the disease degree and inflammatory response in rats with pulmonary fibrosis. Its mechanism may be achieved by regulating Smurf2.
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- Liu YM, Nepali K and Liou JP: Idopathic Pulmonary Fibrosis:current status, recent progress and emerging targets. J Med Chem 60: 527, 2017.
- Bahmer T, Kirsten AM, Waschki B, Rabe KF, Magnussen H, Kirsten D, Gramm M, Hummler S, Brunnemer E, Kreuter M, et al: Prognosis and longitudinal changes of physical activity in idiopathic pulmonary fibrosis. BMC Pulm Med 17: 104, 2017.
- Dowman LM, Mcdonald CF, Bozinovski S, Vlahos R, Gillies R, Pouniotis D, Hill CJ, Goh NSL and Holland AE: Greater endurance capacity and improved dyspnoea with acute oxygen supplementation in idiopathic pulmonary fibrosis patients without resting hypoxaemia. Respirology, 22: 957-964, 2017.
- Kaur A, Mathai SK and Schwartz DA: Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment. Front Med (Lausanne) 4: 154, 2017.
- Liu LJ and Qian H: Up-regulation of miR-21 promotes cell prolifera- tion and collagen synthesis in pulmonary fibroblasts. Chin J Cell Mol Immunol,31: 918 -922, 2015.
- Díazpiña G, Ordoñezrazo RM, Montes E, Páramo I, Becerril C, Salgado A, Santibañez-Salgado JA, Maldonado M and Ruiz V: The Role of ADAR1 and ADAR2 in the Regulation of miRNA-21 in Idiopathic Pulmonary Fibrosis. Lung 196 201: 1-8, 2018.
- Zhao N, Sun H, Sun B, Zhu D, Zhao X, Wang Y, Gu Q, Dong X, Liu F, Zhang Y, et al: miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT:an essential role for Twist-1 in HCC. Sci Rep 6: 23091, 2016.
- Salah Z, Arafeh R, Maximov V, Galasso M, Khawaled S, Abou-Sharieha S, Volinia S, Jones KB, Croce CM and Aqeilan RI: miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells. Oncotarget 6: 4920 - 4935, 2015.
- Cui H, Banerjee S, Xie N, Ge J, Liu RM, Matalon S, Thannickal VJ and Liu G: miR-27a-3p is a negative regu- lator of lung fibrosis by targeting myofibroblast differentiation. Am J Respir Cell Mol Biol 54: 843 -852, 2016.
- Cai Y, Zhou CH, Fu D and Shen XZ: Overexpression of Smad ubiquitin regu- latory factor 2 suppresses transforming growth factor-β mediated liv- er fibrosis. J Dig Dis 13: 327-334, 2012.
- Robinson PA and Ardley HC: Ubiquitin- protein ligases. J Cell Sci 117: 5191-5194, 2004.
- Yan QU, Zhang C, Jia YL, et al: Rhein attenuates bleomycin-induced rats pulmonary fibrosis through TGF-β1/Smad pathway by inhibiting miR-21 expression. Chinese Journal of Pathophysiology 2017.
- Liu L, Qian H, Yin H, He J, Zhang P and Wang Z: Unsaturated fatty acid of Actinidia chinesis Planch seed oil enhances the antioxidative stress ability of rats with pulmonary fibrosis through activating Keap 1 / Nrf 2 signaling pathway. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 32: 479-483, 2016.
- Martinez FJ, Chisholm A, Collard HR, Flaherty KR, Myers J, Raghu G, Walsh SL, White ES and Richeldi L: The diagnosis of idiopathic pulmonary fibrosis:current and future approaches. Lancet Respir Med 5: 61-71, 2017.
- King CS and Nathan SD: Idiopathic pulmonary fibrosis:effects and optimal management of comorbidities. Lancet Respir Med 5: 2017.
- Zhang Q, Ye H, Xiang F, Song LJ, Zhou LL, Cai PC, Zhang JC, Yu F, Shi HZ, Su Y, et al: miR-18a-5p Inhibits Sub-pleural Pulmonary Fibrosis by Targeting TGF-β Receptor II. Mol Ther 25: 728, 2017.
- Zhou L, Liang X, Zhang L, Yang L, Nagao N, Wu H, Liu C, Lin S, Cai G and Liu J: miR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2 [J/OL]. Oncotarget 7: 51943 - 51954, 2016.
- Knudsen L, Ruppert C and Ochs M: Tissue remodelling in pulmonary fibrosis. Cell Tissue Re 367: 607 - 626, 2017.
- Guan S and Zhou J: Frizzled-7 mediates TGF-β-induced pulmonary fibrosis by transmitting non-canonical Wnt signaling. Exp Cell Res 359: 226-234, 2017.
- Wu B, Guo B, Kang J, Deng X, Fan Y, Zhang X and Ai K: Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-β-induced tumor formation.Tumour Biol: 1-15, 2016.
- Ganji A, Mosayebzadeh H, Varasteh A, Moghadam M and Sankian M: The effects of WW2/WW3 domains of Smurf2 molecule on TGF-βsignaling and arginase I gene expression. Cell Biol Int 39: 690-695, 2015.
- Mutlu GM, Budinger GR, Wu M, Lam AP, Zirk A, Rivera S, Urich D, Chiarella SE, Go LH, Ghosh AK, et al: Proteasomal inhibition after injury prevents fibrosis by modulating TGF-β(1)signalling. Thorax 67: 139-146, 2012.
- Li L C, Xu L, Hu Y, Cui WJ, Cui WH, Zhou WC and Kan LD: Astragaloside IV Improves Bleomycin-Induced Pulmonary Fibrosis in Rats by Attenuating Extracellular Matrix Deposition. Front Pharmacol 8: 513, 2017.
- Beach TA, Johnston CJ, Groves AM, Williams JP and Finkelstein JN: Radiation induced pulmonary fibrosis as a model of progressive fibrosis:Contributions of DNA damage, inflammatory response and cellular senescence genes. Exp Lung Res 43: 1, 2017.
- Yang J, Cao S and Zhang M: Effect of Smad ubiquitination regulatory factor 2 on TGF-β1-induced activation in lung fibroblasts and its molecular mechanism. Journal of Jilin University 30: 129-151, 2015.
References
Liu YM, Nepali K and Liou JP: Idopathic Pulmonary Fibrosis:current status, recent progress and emerging targets. J Med Chem 60: 527, 2017.
Bahmer T, Kirsten AM, Waschki B, Rabe KF, Magnussen H, Kirsten D, Gramm M, Hummler S, Brunnemer E, Kreuter M, et al: Prognosis and longitudinal changes of physical activity in idiopathic pulmonary fibrosis. BMC Pulm Med 17: 104, 2017.
Dowman LM, Mcdonald CF, Bozinovski S, Vlahos R, Gillies R, Pouniotis D, Hill CJ, Goh NSL and Holland AE: Greater endurance capacity and improved dyspnoea with acute oxygen supplementation in idiopathic pulmonary fibrosis patients without resting hypoxaemia. Respirology, 22: 957-964, 2017.
Kaur A, Mathai SK and Schwartz DA: Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment. Front Med (Lausanne) 4: 154, 2017.
Liu LJ and Qian H: Up-regulation of miR-21 promotes cell prolifera- tion and collagen synthesis in pulmonary fibroblasts. Chin J Cell Mol Immunol,31: 918 -922, 2015.
Díazpiña G, Ordoñezrazo RM, Montes E, Páramo I, Becerril C, Salgado A, Santibañez-Salgado JA, Maldonado M and Ruiz V: The Role of ADAR1 and ADAR2 in the Regulation of miRNA-21 in Idiopathic Pulmonary Fibrosis. Lung 196 201: 1-8, 2018.
Zhao N, Sun H, Sun B, Zhu D, Zhao X, Wang Y, Gu Q, Dong X, Liu F, Zhang Y, et al: miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT:an essential role for Twist-1 in HCC. Sci Rep 6: 23091, 2016.
Salah Z, Arafeh R, Maximov V, Galasso M, Khawaled S, Abou-Sharieha S, Volinia S, Jones KB, Croce CM and Aqeilan RI: miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells. Oncotarget 6: 4920 - 4935, 2015.
Cui H, Banerjee S, Xie N, Ge J, Liu RM, Matalon S, Thannickal VJ and Liu G: miR-27a-3p is a negative regu- lator of lung fibrosis by targeting myofibroblast differentiation. Am J Respir Cell Mol Biol 54: 843 -852, 2016.
Cai Y, Zhou CH, Fu D and Shen XZ: Overexpression of Smad ubiquitin regu- latory factor 2 suppresses transforming growth factor-β mediated liv- er fibrosis. J Dig Dis 13: 327-334, 2012.
Robinson PA and Ardley HC: Ubiquitin- protein ligases. J Cell Sci 117: 5191-5194, 2004.
Yan QU, Zhang C, Jia YL, et al: Rhein attenuates bleomycin-induced rats pulmonary fibrosis through TGF-β1/Smad pathway by inhibiting miR-21 expression. Chinese Journal of Pathophysiology 2017.
Liu L, Qian H, Yin H, He J, Zhang P and Wang Z: Unsaturated fatty acid of Actinidia chinesis Planch seed oil enhances the antioxidative stress ability of rats with pulmonary fibrosis through activating Keap 1 / Nrf 2 signaling pathway. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 32: 479-483, 2016.
Martinez FJ, Chisholm A, Collard HR, Flaherty KR, Myers J, Raghu G, Walsh SL, White ES and Richeldi L: The diagnosis of idiopathic pulmonary fibrosis:current and future approaches. Lancet Respir Med 5: 61-71, 2017.
King CS and Nathan SD: Idiopathic pulmonary fibrosis:effects and optimal management of comorbidities. Lancet Respir Med 5: 2017.
Zhang Q, Ye H, Xiang F, Song LJ, Zhou LL, Cai PC, Zhang JC, Yu F, Shi HZ, Su Y, et al: miR-18a-5p Inhibits Sub-pleural Pulmonary Fibrosis by Targeting TGF-β Receptor II. Mol Ther 25: 728, 2017.
Zhou L, Liang X, Zhang L, Yang L, Nagao N, Wu H, Liu C, Lin S, Cai G and Liu J: miR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2 [J/OL]. Oncotarget 7: 51943 - 51954, 2016.
Knudsen L, Ruppert C and Ochs M: Tissue remodelling in pulmonary fibrosis. Cell Tissue Re 367: 607 - 626, 2017.
Guan S and Zhou J: Frizzled-7 mediates TGF-β-induced pulmonary fibrosis by transmitting non-canonical Wnt signaling. Exp Cell Res 359: 226-234, 2017.
Wu B, Guo B, Kang J, Deng X, Fan Y, Zhang X and Ai K: Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-β-induced tumor formation.Tumour Biol: 1-15, 2016.
Ganji A, Mosayebzadeh H, Varasteh A, Moghadam M and Sankian M: The effects of WW2/WW3 domains of Smurf2 molecule on TGF-βsignaling and arginase I gene expression. Cell Biol Int 39: 690-695, 2015.
Mutlu GM, Budinger GR, Wu M, Lam AP, Zirk A, Rivera S, Urich D, Chiarella SE, Go LH, Ghosh AK, et al: Proteasomal inhibition after injury prevents fibrosis by modulating TGF-β(1)signalling. Thorax 67: 139-146, 2012.
Li L C, Xu L, Hu Y, Cui WJ, Cui WH, Zhou WC and Kan LD: Astragaloside IV Improves Bleomycin-Induced Pulmonary Fibrosis in Rats by Attenuating Extracellular Matrix Deposition. Front Pharmacol 8: 513, 2017.
Beach TA, Johnston CJ, Groves AM, Williams JP and Finkelstein JN: Radiation induced pulmonary fibrosis as a model of progressive fibrosis:Contributions of DNA damage, inflammatory response and cellular senescence genes. Exp Lung Res 43: 1, 2017.
Yang J, Cao S and Zhang M: Effect of Smad ubiquitination regulatory factor 2 on TGF-β1-induced activation in lung fibroblasts and its molecular mechanism. Journal of Jilin University 30: 129-151, 2015.