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http://dx.doi.org/10.14348/molcells.2018.2193

Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset  

Qi, You-Fei (Department of Vascular Surgery, the Second Xiang-ya Hospital, Central South University)
Shu, Chang (Department of Vascular Surgery, the Second Xiang-ya Hospital, Central South University)
Xiao, Zhan-Xiang (Department of Vascular Surgery, Hainan General Hospital)
Luo, Ming-Yao (Center of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College)
Fang, Kun (Center of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College)
Guo, Yuan-Yuan (Department of Vascular Surgery, Fuwai Yunnan Cardiovascular Hospital)
Zhang, Wen-Bo (Department of Vascular Surgery, Hainan General Hospital)
Yue, Jie (Department of Vascular Surgery, Hainan General Hospital)
Publication Information
Molecules and Cells / v.41, no.3, 2018 , pp. 198-206 More about this Journal
Abstract
Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.
Keywords
aortic dissection (AD); aortic smooth muscle cells (ASMC); miR-144-3p; tropoelastin (TE);
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1 Ray, J.L., Leach, R., Herbert, J.M., and Benson, M. (2001). Isolation of vascular smooth muscle cells from a single murine aorta. Methods Cell Sci. 23, 185-188.   DOI
2 Sato, F., Seino-Sudo, R., Okada, M., Sakai, H., Yumoto, T., and Wachi, H. (2017). Lysyl Oxidase Enhances the Deposition of Tropoelastin through the Catalysis of Tropoelastin Molecules on the Cell Surface. Biol. Pharm. Bull. 40, 1646-1653.   DOI
3 Segreto, A., Chiusaroli, A., De Salvatore, S., and Bizzarri, F. (2014). Biomarkers for the diagnosis of aortic dissection. J. Card Surg. 29, 507-511.   DOI
4 Seok, H., Ham, J., Jang, E.S., and Chi, S.W. (2016). MicroRNA target recognition: insights from transcriptome-wide non-canonical interactions. Mol. Cells 39, 375-381.   DOI
5 Shao, Y., Li, P., Zhu, S.T., Yue, J.P., Ji, X.J., Ma, D., Wang, L., Wang, Y.J., Zong, Y., Wu, Y.D., et al. (2016). MiR-26a and miR-144 inhibit proliferation and metastasis of esophageal squamous cell cancer by inhibiting cyclooxygenase-2. Oncotarget 7, 15173-15186.
6 Stone, P.J., Lucey, E.C., Snider, G.L., and Franzblau, C. (1997). Distribution of elastin in hamsters and the turnover rates of different elastin pools. Proc. Soc. Exp. Biol. Med. 215, 94-101.   DOI
7 Sudo, R., Sato, F., Azechi, T., and Wachi, H. (2015). MiR-29-mediated elastin down-regulation contributes to inorganic phosphorus-induced osteoblastic differentiation in vascular smooth muscle cells. Genes Cells 20, 1077-1087.   DOI
8 Vega-Badillo, J., Gutierrez-Vidal, R., Hernandez-Perez, H.A., Villamil-Ramirez, H., Leon-Mimila, P., Sanchez-Munoz, F., Moran-Ramos, S., Larrieta-Carrasco, E., Fernandez-Silva, I., Mendez-Sanchez, N., et al. (2016). Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects. Liver Int. 6, 1383-1391.
9 Zhang, P., Huang, A., Ferruzzi, J., Mecham, R.P., Starcher, B.C., Tellides, G., Humphrey, J.D., Giordano, F.J., Niklason, L.E., and Sessa, W.C. (2012). Inhibition of microRNA-29 enhances elastin levels in cells haploinsufficient for elastin and in bioengineered vessels--brief report. Arterioscler Thromb. Vasc. Biol. 32, 756-759.   DOI
10 Zhang, S.Y., Lu, Z.M., Lin, Y.F., Chen, L.S., Luo, X.N., Song, X.H., Chen, S.H., and Wu, Y.L. (2016). miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma. Oncotarget 7, 11637-11650.
11 Ivey, K.N., Muth, A., Arnold, J., King, F.W., Yeh, R.F., Fish, J.E., Hsiao, E.C., Schwartz, R.J., Conklin, B.R., Bernstein, H.S., et al. (2008). MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell 2, 219-229.   DOI
12 Agarwal, V., Bell, G.W., Nam, J.W., and Bartel, D.P. (2015). Predicting effective microRNA target sites in mammalian mRNAs. eLife 4, doi: 10.7554/eLife.05005.   DOI
13 Cao, M.X., Jiang, Y.P., Tang, Y.L., and Liang, X.H. (2017). The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity. Oncotarget 8, 12472-12483.
14 Chuang, T.D., Pearce, W.J., and Khorram, O. (2015). miR-29c induction contributes to downregulation of vascular extracellular matrix proteins by glucocorticoids. Am J Physiol Cell Physiol. 309, C117-125.   DOI
15 Ekman, M., Bhattachariya, A., Dahan, D., Uvelius, B., Albinsson, S., and Sward, K. (2013). Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness. PLoS One 8, e82308.   DOI
16 Forman, J.J., Legesse-Miller, A., and Coller, H.A. (2008). A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A 105, 14879-14884.   DOI
17 Helbig, G., and Krzemien, S. (2004). Clinical significance of elastin turnover--focus on diseases affecting elastic fibres. Wiad Lek 57, 360-363.
18 Isselbacher, E.M., Lino Cardenas, C.L., and Lindsay, M.E. (2016). Hereditary Influence in Thoracic Aortic Aneurysm and Dissection. Circulation 133, 2516-2528.   DOI
19 Janoff, A. (1983). Do neutrophils play a major role in elastin turnover of normal tissues? Am. Rev. Respir. Dis. 127, 782-783.
20 Jiang, W., Zhang, Z., Yang, H., Lin, Q., Han, C., and Qin, X. (2017). The involvement of miR-29b-3p in arterial calcification by targeting matrix metalloproteinase-2. BioMed. Res. Int. 2017, 6713606.
21 Jiang, X., Shan, A., Su, Y., Cheng, Y., Gu, W., Wang, W., Ning, G., and Cao, Y. (2015). miR-144/451 Promote cell proliferation via targeting PTEN/AKT pathway in insulinomas. Endocrinology 156, 2429-2439.   DOI
22 Li, Q. and Gregory, R.I. (2008). MicroRNA regulation of stem cell fate. Cell Stem Cell 2, 195-196.   DOI
23 Okamura, H., Emrich, F., Trojan, J., Chiu, P., Dalal, A.R., Arakawa, M., Sato, T., Penov, K., Koyano, T., Pedroza, A., et al. (2017). Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model. Physiol. Rep. 5, pii: e13257.   DOI
24 Maegdefessel, L., Azuma, J., Toh, R., Merk, D.R., Deng, A., Chin, J.T., Raaz, U., Schoelmerich, A.M., Raiesdana, A., Leeper, N.J., et al. (2012). Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J. Clin. Invest. 122, 497-506.   DOI
25 Mallat, Z., Tedgui, A., and Henrion, D. (2016). Role of microvascular tone and extracellular matrix contraction in the regulation of interstitial fluid: implications for aortic dissection. Arterioscler. Thromb. Vasc. Biol. 36, 1742-1747.   DOI
26 Merk, D.R., Chin, J.T., Dake, B.A., Maegdefessel, L., Miller, M.O., Kimura, N., Tsao, P.S., Iosef, C., Berry, G.J., Mohr, F.W., et al. (2012). miR-29b participates in early aneurysm development in Marfan syndrome. Circ. Res. 110, 312-324.   DOI
27 Morello, F., Piler, P., Novak, M., and Kruzliak, P. (2014). Biomarkers for diagnosis and prognostic stratification of aortic dissection: challenges and perspectives. Biomarkers Med. 8, 931-941.   DOI
28 Nygaard, R.H., Maynard, S., Schjerling, P., Kjaer, M., Qvortrup, K., Bohr, V.A., Rasmussen, L.J., Jemec, G.B., and Heidenheim, M. (2016). Acquired localized cutis laxa due to increased elastin turnover. Case Rep. Dermatol. 8, 42-51.   DOI
29 Ott, C.E., Grunhagen, J., Jager, M., Horbelt, D., Schwill, S., Kallenbach, K., Guo, G., Manke, T., Knaus, P., Mundlos, S., et al. (2011). MicroRNAs differentially expressed in postnatal aortic development downregulate elastin via 3′ UTR and coding-sequence binding sites. PLoS One 6, e16250.   DOI
30 Papagiannakopoulos, T., and Kosik, K.S. (2009). MicroRNA-124: micromanager of neurogenesis. Cell Stem Cell 4, 375-376.   DOI
31 Patel, P.D., and Arora, R.R. (2008). Pathophysiology, diagnosis, and management of aortic dissection. Ther Adv Cardiovasc Dis 2, 439-468.   DOI