KRT1 gene silencing ameliorates myocardial ischemia-reperfusion injury via the activation of the Notch signaling pathway in mouse models.

Abstract

Myocardial ischemia and reperfusion injury (MIRI) includes major drawbacks, such as excessive formation of free radicals and also overload of calcium, which lead to cell death, tissue scarring, and remodeling. The current study aims to explore whether KRT1 silencing may ameliorate MIRI via the Notch signaling pathway in mouse models. Myocardial tissues were used for the determination of the positive rate of KRT1 protein expression, apoptosis of myocardial cells, creatine kinase (CK) and lactate dehydrogenase (LDH) expression, expression of related biomarkers as well as myocardial infarction area. The transfected myocardial cells were treated with KRT1-siRNA, Jagged1, and DAPT (inhibitor of Notch-1 signaling pathway). The expression of KRT1, NICD, Hes1, Bcl-2, and Bax protein was detected. The MTT assay was applied for cell proliferation and flow cytometry was used for cell apoptosis. Mice with MIRI had a higher positive rate of KRT1 protein expression, apoptosis of myocardial cells, CK and LDH expression, myocardial infarction area, increased expression of MDA, NO, SDH, IL-1, IL-6, TNF-α, CRP, KRT1, Bax protein, CK, and LDH, and decreased expression of SOD, NICD, Hes1, and Bcl-2. The downregulation of KRT1 led to decreased expression of KRT1 and Bax protein, increased expression of NICD, Hes1, and Bcl-2, decreased cell apoptosis, and improved cell proliferation. The inhibition of the Notch signaling pathway leads to reduced expression of Bax, increased expression of NICD, Hes1, and Bcl 2, and also decreased cell apoptosis and increased cell proliferation. Our data conclude that KRT1 silencing is able to make MIRI better by activating the Notch signaling pathway in mice.

• Authors: Hong-Cheng Fang, Bao-Quan Wu, Yun-Ling Hao, Ying Luo, Hong-Lei Zhao, Wen-Ying Zhang, Zhi-Ling Zhang, Jin-Jie Liang, Wei Liu, Xie-Hui Chen
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 4 Pg. 3634-3646 (04 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30191968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Apoptosis Regulatory Proteins
• Inflammation Mediators
• Keratin-1
• Krt1 protein, mouse
• Receptors, Notch

Topics

• Animals
• Apoptosis
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cell Proliferation
• Cells, Cultured
• Disease Models, Animal
• Female
• Gene Silencing
• Inflammation Mediators (metabolism)
• Keratin-1 (genetics, metabolism)
• Male
• Mice, Inbred C57BL
• Myocardial Reperfusion Injury (genetics, metabolism, pathology, prevention & control)
• Myocytes, Cardiac (metabolism, pathology)
• Oxidative Stress
• Rats, Sprague-Dawley
• Receptors, Notch (genetics, metabolism)
• Signal Transduction