Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition

Zheng, Xiaolin; Peng, Meng; Li, Yan; Wang, Xule; Lu, Wenjie; Wang, Xi; Shan, Yingguang; Li, Ran; Gao, Lu; Qiu, Chunguang

doi:10.7150/ijbs.35736



Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

Global reach, higher impact

Full Text | PDF

Int J Biol Sci 2019; 15(11):2393-2407. doi:10.7150/ijbs.35736 This issue Cite

Research Paper

Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition

Xiaolin Zheng, Meng Peng, Yan Li, Xule Wang, Wenjie Lu, Xi Wang, Yingguang Shan, Ran Li, Lu Gao^✉, Chunguang Qiu^✉

Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Citation:

Zheng X, Peng M, Li Y, Wang X, Lu W, Wang X, Shan Y, Li R, Gao L, Qiu C. Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition. Int J Biol Sci 2019; 15(11):2393-2407. doi:10.7150/ijbs.35736. https://www.ijbs.com/v15p2393.htm

Other styles

Abstract

Cathelicidin-related antimicrobial peptide (CRAMP), antimicrobial peptide, was reported to protect against myocardial ischemia/reperfusion injury. In the pathology of diabetic cardiomyopathy, endothelial-to-mesenchymal transition (EndMT) results from hyperglycemia-induced endothelial injury, leading to cardiac fibrosis. This study aims to evaluate the effect of CRAMP on EndMT and cardiac fibrosis on diabetic mice heart. Mice were subjected to streptozotocin to induce diabetes. CRAMP was administered by intraperitoneal injection (1 or 8 mg/kg/d) for 4 weeks from 12 weeks till 16 weeks after final streptozotocin injection. Cardiac dysfunction was observed in diabetic mice. Only 8 mg/kg/d CRAMP treatment proved cardiac function. Increased EndMT and fibrosis level were also observed in diabetic mice heart. 8mg/kg CRAMP inhibited EndMT and fibrosis level in diabetic mice. Mouse heart endothelial cells (MHECs) were treated with CRAMP and exposed to high glucose. Hyperglycemia-induced EndMT in MHECs was also attenuated by CRAMP treatment. Activation of TGFβ/Smad signalling was increased in diabetic mice heart tissue and hyperglycemia stimulated MHECs, which was prevented following CRAMP treatment. Activation of AMPKa1/mTOR showed similar changes. AMPKa1 siRNA abrogated the effects of CRAMP in MHECs. TGFβ/Smad inhibitor LY2109761 and AMPKa agonist AIRCA mimic the effect of CRAMP. In summary, CRAMP can inhibit EndMT, cardiac fibrosis and protect against diabetic cardiomyopathy by regulating AMPKa1/TGFβ signalling.

Keywords: Cathelicidin-related antimicrobial peptide, diabetic cardiomyopathy, EndMT, AMPKa1

Citation styles

APA

Zheng, X., Peng, M., Li, Y., Wang, X., Lu, W., Wang, X., Shan, Y., Li, R., Gao, L., Qiu, C. (2019). Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition. International Journal of Biological Sciences, 15(11), 2393-2407. https://doi.org/10.7150/ijbs.35736.

ACS

Zheng, X.; Peng, M.; Li, Y.; Wang, X.; Lu, W.; Wang, X.; Shan, Y.; Li, R.; Gao, L.; Qiu, C. Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition. Int. J. Biol. Sci. 2019, 15 (11), 2393-2407. DOI: 10.7150/ijbs.35736.

NLM

CSE

Zheng X, Peng M, Li Y, Wang X, Lu W, Wang X, Shan Y, Li R, Gao L, Qiu C. 2019. Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition. Int J Biol Sci. 15(11):2393-2407.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.