Modulation of Vascular Smooth Muscle Cell Phenotype by High Mobility Group AT-Hook 1
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초록
Objective: The purpose of this study is to examine the effect of high mobility group AT-hook 1 (HMGA1) on the phenotyptic change of vascular smooth muscle cells (VSMCs). Methods: Gene silencing and overexpression of HMGA1 were introduced to evaluate the effect of HMGA1 expression on the phenotypic change of VSMCs. Marker gene expression of VSMCs was measured by promoter assay, quantitative polymerase chain reaction, and western blot analysis. Common left carotid artery ligation model was used to establish in vivo neointima formation. Results: HMGA1 was expressed strongly in the synthetic type of VSMCs and significantly downregulated during the differentiation of VSMCs. Silencing of HMGA1 in the synthetic type of VSMCs enhanced the expression of contractile marker genes thereby enhanced angiotensin II (Ang II)-dependent contraction, however, significantly suppressed proliferation and migration. Stimulation of contractile VSMCs with platelet-derived growth factor (PDGF) enhanced HMGA1 expression concomitant with the downregulation of marker gene expression which was blocked significantly by the silencing of HMGA1. Silencing of HMGA1 retained the Ang II-dependent contractile function, which was curtailed by PDGF stimulation, however, overexpression of HMGA1 in the contractile type of VSMCs suppressed marker gene expression. Proliferation and migration were enhanced significantly by the overexpression of HMGA1. Furthermore, the Ang II-dependent contraction was reduced significantly by the overexpression of HMGA1. Finally, the expression of HMGA1 was enhanced significantly in the ligated artery, especially in the neointima area. Conclusion: HMGA1 plays an essential role in the phenotypic modulation of VSMCs. Therefore, paracrine factors such as PDGF may affect vascular remodeling through the regulation of HMGA1.
Abstract
Objective: The purpose of this study is to examine the effect of high mobility group AT-hook 1 (HMGA1) on the phenotyptic change of vascular smooth muscle cells (VSMCs). Methods: Gene silencing and overexpression of HMGA1 were introduced to evaluate the effect of HMGA1 expression on the phenotypic change of VSMCs. Marker gene expression of VSMCs was measured by promoter assay, quantitative polymerase chain reaction, and western blot analysis. Common left carotid artery ligation model was used to establish in vivo neointima formation. Results: HMGA1 was expressed strongly in the synthetic type of VSMCs and significantly downregulated during the differentiation of VSMCs. Silencing of HMGA1 in the synthetic type of VSMCs enhanced the expression of contractile marker genes thereby enhanced angiotensin II (Ang II)-dependent contraction, however, significantly suppressed proliferation and migration. Stimulation of contractile VSMCs with platelet-derived growth factor (PDGF) enhanced HMGA1 expression concomitant with the downregulation of marker gene expression which was blocked significantly by the silencing of HMGA1. Silencing of HMGA1 retained the Ang II-dependent contractile function, which was curtailed by PDGF stimulation, however, overexpression of HMGA1 in the contractile type of VSMCs suppressed marker gene expression. Proliferation and migration were enhanced significantly by the overexpression of HMGA1. Furthermore, the Ang II-dependent contraction was reduced significantly by the overexpression of HMGA1. Finally, the expression of HMGA1 was enhanced significantly in the ligated artery, especially in the neointima area. Conclusion: HMGA1 plays an essential role in the phenotypic modulation of VSMCs. Therefore, paracrine factors such as PDGF may affect vascular remodeling through the regulation of HMGA1.
참고문헌 (31)
- Steucke KE, "Vascular smooth muscle cell functional contractility depends on extracellular mechanical properties", J Biomech, 48, pp.3044~3051 (2015)
- Rovner AS, "Expression of smooth muscle and nonmuscle myosin heavy chains in cultured vascular smooth muscle cells", J Biol Chem, 261, pp.14740~14745 (1986)
- Owens GK, "Molecular control of vascular smooth muscle cell differentiation", Acta Physiol Scand, 164, pp.623~635 (1998)
- Gomez D, "Smooth muscle cell phenotypic switching in atherosclerosis", Cardiovasc Res, 95, pp.156~164 (2012)
- Zhang MJ, "An overview of potential molecular mechanisms involved in VSMC phenotypic modulation", Histochem Cell Biol, 145, pp.119~130 (2016)
- 노종성, "Damage-Associated Molecular Patterns in Inflammatory Diseases", Immune Network, 18(4), pp.1~14 (2018), 대한면역학회[DOI]
- Andrae J, "Role of platelet-derived growth factors in physiology and medicine", Genes Dev, 22, pp.1276~1312 (2008)
- Hirschi KK, "PDGF, TGF-β, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1", 2 cells and their differentiation to a smooth muscle fate, 1998, pp.141, 805~814
- Kaplan-Albuquerque N, "Patterns of gene expression differentially regulated by platelet-derived growth factor and hypertrophic stimuli in vascular smooth muscle cells : markers for phenotypic modulation and response to injury", J Biol Chem, 280, pp.19966~19976 (2005)
- Egan CG, "PDGF-induced signaling in proliferating and differentiated vascular smooth muscle : effects of altered intracellular Ca2+ regulation", Cardiovasc Res, 67, pp.308~316 (2005)
- Lindqvist A, "Platelet-derived growth factor receptors expressed in response to injury of differentiated vascular smooth muscle in vitro : effects on Ca2+ and growth signals", Acta Physiol Scand, 173, pp.175~184 (2001)
- Wan W, "PDGFR-β modulates vascular smooth muscle cell phenotype via IRF-9", SIRT-1, J Cereb Blood Flow Metab, pp.2019, 39[DOI]
- Wang Y, "HMGA1 in cancer : cancer classification by location", J Cell Mol Med, 23, pp.2293~2302 (2019)
- Sumter TF, "The high mobility group A1(HMGA1)transcriptome in cancer and development", Curr Mol Med, 16, pp.353~393 (2016)
- Arnoldo L, "A novel mechanism of post-translational modulation of HMGA functions by the histone chaperone nucleophosmin", Sci Rep, 5, pp.8552~ (2015)
- Sgarra R, "High mobility group A(HMGA)proteins : molecular instigators of breast cancer onset and progression", Biochim Biophys Acta Rev Cancer, 1869, pp.216~229 (2018)
- Pierantoni GM, "Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities", Cell Cycle, 15, pp.812~818 (2016)
- Liau SS, "HMGA1 is a determinant of cellular invasiveness and in vivo metastatic potential in pancreatic adenocarcinoma", Cancer Res, 66, pp.11613~11622 (2006)
- Yun SJ, "Akt1 isoform modulates phenotypic conversion of vascular smooth muscle cells", Biochim Biophys Acta, 1842, pp.2184~2192 (2014)
- Ha JM, "Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1", Biochem Biophys Res Commun, 464, pp.57~62 (2015)
- Zhang X, "Phenotypic transformation of smooth muscle cells from porcine coronary arteries is associated with connexin 43", Mol Med Rep, 14, pp.41~48 (2016)
- Côrtes SF, "Changes in angiotensin II receptor density and calcium handling during proliferation in SHR aortic myocytes", Am J Physiol, 271, pp.H2330~H2338 (1996)
- Wood LJ, "The oncogenic properties of the HMG-I gene family", Cancer Res, 60, pp.4256~4261 (2000)
- Fedele M, "Truncated and chimeric HMGI-C genes induce neoplastic transformation of NIH3T3 murine fibroblasts", Oncogene, 17, pp.413~418 (1998)
- Fedele M, "Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone", prolactin cell pituitary adenomas and natural killer cell lymphomas, 2005, pp.24, 3427~3435
- Foti D, "Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice", Nat Med, 11, pp.765~773 (2005)
- Federico A, "Hmga1", Hmga2 double knock-out mice display a"superpygmy"phenotype, 2014, pp.3, 372~378
- Balasubramaniam V, "Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus", Am J Physiol Lung Cell Mol Physiol, 284, pp.L826~L833 (2003)
- Zhang Y, "Expression of platelet-derived growth factor in the vascular walls of patients with lower extremity arterial occlusive disease", Exp Ther Med, 9, pp.1223~1228 (2015)
- Zhang Q, "HMGA1 mediated high-glucose-induced vascular smooth muscle cell proliferation in diabetes mellitus : association between PI3K", Akt signaling and HMGA1 expression, 2018, pp.37, 389~397
- Qiu H, "Regulatory axis of miR-195", 497 and HMGA1-Id3governs muscle cell proliferation and differentiation, 2017, pp.13, 157~166