| First Author | Ji L | Year | 2024 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1870 |
| Issue | 1 | Pages | 166900 |
| PubMed ID | 37778481 | Mgi Jnum | J:341990 |
| Mgi Id | MGI:7542626 | Doi | 10.1016/j.bbadis.2023.166900 |
| Citation | Ji L, et al. (2023) Blockage of DCLK1 in cardiomyocytes suppresses myocardial inflammation and alleviates diabetic cardiomyopathy in streptozotocin-induced diabetic mice. Biochim Biophys Acta Mol Basis Dis 1870(1):166900 |
| abstractText | Diabetic cardiomyopathy (DCM) is a pathophysiological condition triggered by diabetes mellitus and can lead to heart failure. Doublecortin-like kinase protein 1 (DCLK1) is a multifunctional protein kinase involved in the regulation of cell proliferation, differentiation, survival, and migration. Current studies on DCLK1 mainly focus on cancer development; however, its role in non-tumor diseases such as DCM is yet to be deciphered. Our analysis revealed that DCLK1 was upregulated in cardiomyocytes of streptozotocin (STZ)-induced type 1 diabetic mouse, suggesting a correlation between DCLK1 and DCM progression. It was further demonstrated that either cardiomyocyte-specific DCLK1 knockout or pharmacological DCLK1 inhibitor DCLK1-IN-1 significantly alleviated cardiac hypertrophy and fibrosis in STZ-induced diabetic mice. RNA-seq analysis of heart tissues revealed that DCLK1 regulated the nuclear factor kappa B (NF-kappaB)-mediated inflammatory response in DCM. In vitro, DCLK1 activated NF-kappaB and the inflammatory response by inducing the IKKbeta phosphorylation in high-concentration glucose (HG)-challenged cardiomyocytes. DCLK1-IN-1 also prevented HG-induced IKKbeta/NF-kappaB activation and inflammatory injuries in cardiomyocytes. In conclusion, this study highlights the novel role of cardiomyocyte DCLK1 in regulating IKKbeta/NF-kappaB, which aggravates inflammation to promote the pathogenesis of DCM. DCLK1 may serve as a new target for DCM treatment. |
