Abstract
The activated renin–angiotensin–aldosterone system modulates several metabolic pathways that contribute to left ventricular hypertrophy and heart failure. In this metabolic system, angiotensin II modulates heart morphophysiological changes triggered by a series of inflammatory and pro-inflammatory responses; however, the fine tuning associated with the control of this biochemical pathway remains unknown. Here, we investigated elements involved in the post-transcriptional regulation of the pro-inflammatory environment in the H9c2 cardiac cell line, focusing on miRNA elements that modulate PTEN expression. A cellular model of investigation was established and the miR-315-5p was identified as a novel element targeting PTEN in this cardiac cell line, thereby controlling the protein level. This interconnected pathway contributes to the control of the pro-inflammatory environment in Ang II-treated cells.
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Xu XD, Song XW, Li Q, Wang GK, Jing Q, Qin YW (2012) Attenuation of microRNA-22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy. J Cell Physiol 227:1391–1398
Custodis F, Eberl M, Kilter H, Bohm M, Laufs U (2006) Association of RhoGDIalpha with Rac1 GTPase mediates free radical production during myocardial hypertrophy. Cardiovasc Res 71:342–351
Stuck BJ, Lenski M, Böhm M, Laufs U (2008) Metabolic switch and hypertrophy of cardiomyocytes following treatment with angiotensin II are prevented by AMP-activated protein kinase. J Biol Chem 283:32562–32569
Jia L, Li Y, Xiao C, Du J (2012) Angiotensin II induces inflammation leading to cardiac remodeling. Front Biosci (Landmark Ed) 1:221–231
Bouzegrhane F, Thibault G (2003) Is angiotensin II a proliferative factor of cardiac fibroblasts? Cardiovasc Res 53:304–312
Yokoyama T, Nakano M, Bednarczyk JL, McIntyre BW, Entman M, Mann DL (1997) Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes. Circulation 95:1247–1252
Smeets PJH, Teunissen BEJ, Planavila A, Vogel-van den Bosch H, Willemsen PHM (2008) Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARα and PPARδ. J Biol Chem 283:29109–29118
Purcell NH, Tang G, Yu C, Mercurio F, DiDonato JA, Lin A (2001) Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc Natl Acad Sci USA 98:6668–6673
Haeggstrom JZ, Rinaldo-Matthis A, Wheelock CE, Wetterholm A (2010) Advances in eicosanoid research, novel therapeutic implications. Biochem Biophys Res Commun 396:135–139
Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV (1997) Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356–362
St-Germain ME, Gagnon V, Mathieu I, Parent S, Asselin E (2004) Akt regulates COX-2 mRNA and protein expression in mutated-PTEN human endometrial cancer cells. Int J Oncol 24:1311–1324
Lee SH, Lee YP, Kim SY, Jeong MS, Lee MJ, Kang HW, Jeong HJ, Kim DW, Sohn EJ, Jang SH, Kim YH, Kwon HJ, Cho SW, Park J, Eum WS, Choi SY (2008) Inhibition of LPS-induced cyclooxygenase 2 and nitric oxide production by transduced PEP-1-PTEN fusion protein in Raw 264.7 macrophage cells. Exp Mol Med 40(629):638
Li CJ, Chang JK, Wang GJ, Ho ML (2011) Constitutively expressed COX-2 in osteoblasts positively regulates Akt signal transduction via suppression of PTEN activity. Bone 48:286–297
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress and timing. Cell 113:673–676
Small EM, Olson EN (2011) Pervasive roles of microRNAs in cardiovascular biology. Nature 469:336–342
Olson EN (2014) MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease. Sci Transl Med 6:239ps3
Bush EW, van Rooij E (2014) miR-25 in heart failure. Circ Res 115:610–612
Condorelli G (2014) MicroRNA-29, a mysterious regulator in myocardial fibrosis and circulating miR-29a as biomarker. J Am Coll Cardiol 64:18–25
Nishiguchi T, Imanishi T, Akasaka T (2015) MicroRNAs and cardiovascular diseases. Biomed Res Int 2015:682857–682871
Smeets PJ, Teunissen BE, Planavila A, de Vogel-van den Bosch H, de Vogel-van den Bosch H, Willemsen PH, van der Vusse GJ, van Bilsen M (2008) Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta. J Biol Chem 283:29109–29118
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63
Sambrook J, Fritsch EF, Maniatis T (2001) Molecular cloning: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Inc, New York
Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158
John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS (2004) Human microRNA targets. PLoS Biol 2:e363
Jin W, Reddy MA, Chen Z, Putta S, Lanting L, Kato M, Park JT, Chandra M, Wang C, Tangirala RK, Natarajan R (2012) Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells. J Biol Chem 287:15672–15683
Covey TM, Edes K, Fitzpatrick FA (2007) Akt activation by arachidonic acid metabolism occurs via oxidation and inactivation of PTEN tumor suppressor. Oncogene 26:5784–5792
Ji Y, He Y, Liu L, Zhong X (2010) MiRNA-26b regulates the expression of cyclooxygenase-2 in desferrioxamine-treated CNE cells. FEBS Lett 584:961–967
Vasquez F, Ramaswamy S, Nakamura N, Sellers WR (2000) Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol 20:5010–5018
Torres J, Pulido R (2001) The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem 12(276):993–998
Tamguney T, Stokoe D (2007) New insights into PTEN. J Cell Sci 120:4071–4079
Shao J, Sheng H, Inoue H, Morrow JD, DuBois RN (2000) Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem 275:33951–33956
Acknowledgments
This study was supported by research grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP—2009/07671-2), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (475586/2009-3), and INCT-Nano-Biofarmacêutica
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da Silva, W., dos Santos, R.A.S. & Moraes, K.C.M. Mir-351-5p contributes to the establishment of a pro-inflammatory environment in the H9c2 cell line by repressing PTEN expression. Mol Cell Biochem 411, 363–371 (2016). https://doi.org/10.1007/s11010-015-2598-5
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DOI: https://doi.org/10.1007/s11010-015-2598-5