The effect of HMGA1 in LPS-induced Myocardial Inflammation

Cai, Zhu-Lan; Shen, Bo; Yuan, Yuan; Liu, Chen; Xie, Qing-Wen; Hu, Tong-Tong; Yao, Qi; Wu, Qing-Qing; Tang, Qi-Zhu

doi:10.7150/ijbs.39947

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Int J Biol Sci 2020; 16(11):1798-1810. doi:10.7150/ijbs.39947 This issue Cite

Research Paper

The effect of HMGA1 in LPS-induced Myocardial Inflammation

Zhu-Lan Cai^1,2*, Bo Shen^1,2*, Yuan Yuan^1,2, Chen Liu^1,2, Qing-Wen Xie^1,2, Tong-Tong Hu^1,2, Qi Yao^1,2, Qing-Qing Wu^1,2✉, Qi-Zhu Tang^1,2✉

1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, RP China.
2. Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, RP China.
*These authors contributed equally to this work.

✉ Corresponding authors: Qi-Zhu Tang, Department of Cardiology, Renmin Hospital of Wuhan University; Hubei Key Laboratory of Metabolic and Chronic Diseases; Wuhan University at Jiefang Road 238, Wuhan 430060, RP China; Tel.: +86 27 88073385, Fax: +86 More

Citation:

Cai ZL, Shen B, Yuan Y, Liu C, Xie QW, Hu TT, Yao Q, Wu QQ, Tang QZ. The effect of HMGA1 in LPS-induced Myocardial Inflammation. Int J Biol Sci 2020; 16(11):1798-1810. doi:10.7150/ijbs.39947. https://www.ijbs.com/v16p1798.htm

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Abstract

Aims: The High Mobility Group A1 (HMGA1) proteins, serving as a dynamic regulator of gene transcription and chromatin remodeling, play an influential part in the pathological process of a large number of cardiovascular diseases. However, the precise role of HMGA1 in sepsis induced cardiomyopathy (SIC) remains unintelligible. This research was designed to illustrate the effect of HMGA1 involved in SIC.

Methods and Results: Cardiomyocyte-specific HMGA1 overexpression was obtained using an adeno-associated virus system with intramyocardial injection in mice heart. The model of SIC in mice was constructed via intraperitoneal injection of lipopolysaccharide (LPS) for 6h. H9c2 rat cardiomyocytes was stimulated with LPS for 12h. HMGA1 expression was upregulated in murine inflammatory hearts as well as LPS stimulated H9c2 cardiomyocytes. HMGA1-overexpressing exhibited aggravated cardiac dysfunction, cardiac inflammation as well as cells apoptosis following LPS treatment both in vivo and in vitro experiment. Interestingly, HMGA1 knockdown in H9c2 cardiomyocytes attenuated LPS-induced cardiomyocyte inflammation, but aggravated cell apoptosis. Mechanistically, we found that overexpression of HMGA1 induced increased expression of cyclooxygenase-2 (COX-2). COX-2 inhibitor alleviated the aggravation of inflammation and apoptosis in HMGA1 overexpressed H9c2 cardiomyocytes whereas HMGA1 knockdown induced a reduction in signal transducer and activators of transcription 3 (STAT3) expression. STAT3 agonist reversed HMGA1 silence induced anti-inflammatory effects, while ameliorated cell apoptosis induced by LPS.

Conclusion: In conclusion, our results suggest that overexpression of HMGA1 aggravated cardiomyocytes inflammation and apoptosis by up-regulating COX-2 expression, while silence of HMGA1 expression attenuated inflammation but aggregated cell apoptosis via down-regulation of STAT3.

Keywords: Myocardial inflammation, lipopolysaccharide, HMGA1, cyclooxygenase-2, STAT3

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APA

Cai, Z.L., Shen, B., Yuan, Y., Liu, C., Xie, Q.W., Hu, T.T., Yao, Q., Wu, Q.Q., Tang, Q.Z. (2020). The effect of HMGA1 in LPS-induced Myocardial Inflammation. International Journal of Biological Sciences, 16(11), 1798-1810. https://doi.org/10.7150/ijbs.39947.

ACS

Cai, Z.L.; Shen, B.; Yuan, Y.; Liu, C.; Xie, Q.W.; Hu, T.T.; Yao, Q.; Wu, Q.Q.; Tang, Q.Z. The effect of HMGA1 in LPS-induced Myocardial Inflammation. Int. J. Biol. Sci. 2020, 16 (11), 1798-1810. DOI: 10.7150/ijbs.39947.

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CSE

Cai ZL, Shen B, Yuan Y, Liu C, Xie QW, Hu TT, Yao Q, Wu QQ, Tang QZ. 2020. The effect of HMGA1 in LPS-induced Myocardial Inflammation. Int J Biol Sci. 16(11):1798-1810.

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