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.

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway

“…23 Research has shown that the miR-21/ TLR4/NF-jB pathway takes part in myocardial apoptosis in rats with myocardial ischemia-reperfusion. 24 The current study demonstrated that the levels of miR-21 mRNA were significantly increased as a result of ischaemia-reperfusion in rats and treatment with curcumin reduced the levels of miR-21 mRNA. In addition, the concomitant administration of an inhibitor of miR-21 (antagomir-21) resulted in increased levels of miR-21 mRNA.…”

Retracted: Silencing of keratin 1 inactivates the Notch signaling pathway to inhibit renal interstitial fibrosis and glomerular sclerosis in uremia

“…Additionally, the cell components were mainly concentrated in the nucleus, and molecular functions were primarily concentrated on protein binding (Figure b). Subsequently, KRT1 was found to exert regulatory effect through the Notch signaling pathway (Fang et al, ; Gao et al, ). Immunohistochemistry results displayed that KRT1 expression was evidently upregulated in renal epithelial cells of uremic rats in relation to the sham‐operated rats.…”

“…Therefore, by interacting with the vascular endothelial growth factor pathway, the Notch pathway, whose inactivation serves as a therapeutic insight for diabetic nephropathy treatment, could enhance diabetic kidney disease progression (Seon‐Ho & Katalin, ). Based on the current literature (Fang et al, ; Gao et al, ), which demonstrated that KRT1 has been involved in the Notch signaling pathway, it was hypothesized that KRT1 has the potential to regulate the Notch pathway to affect glomerulosclerosis and kidney dysfunction. In conclusion, in this study, the physiological role of KRT1 silencing and Notch pathway inhibition in uremia was investigated by regulating glomerulosclerosis and kidney dysfunction.…”

iTRAQ‑based proteomic analysis reveals potential regulatory networks in dust mite‑related asthma treated with subcutaneous allergen immunotherapy

“…Keratin family proteins can promote the proliferation of epithelial cells via multiple immune response pathways, and the epidermal cells are known to serve a key role in airway remodeling during asthma (23). Previous research has indicated that KrT1 was involved in the regulation of the notch signaling pathway and affected the repair of vascular endothelial cell damage (24,25). It has been identified that the specific expression of KRT1 affects complex traits (26).…”