| First Author | Tian Y | Year | 2021 |
| Journal | Toxicol Appl Pharmacol | Volume | 427 |
| Pages | 115654 | PubMed ID | 34310909 |
| Mgi Jnum | J:334187 | Mgi Id | MGI:7386965 |
| Doi | 10.1016/j.taap.2021.115654 | Citation | Tian Y, et al. (2021) KLF15 negatively regulates cardiac fibrosis by which SDF-1beta attenuates cardiac fibrosis in type 2 diabetic mice. Toxicol Appl Pharmacol 427:115654 |
| abstractText | Diabetic cardiomyopathy (DCM) is a serious diabetic complication that lacks effective preventive or therapeutic approaches. Wild-type and Klf15 knockout (Klf15-KO) mice were fed with either high fat diet (HFD, 60% kcal from fat) or normal diet (ND, 10% kcal from fat) for 3 months and then injected with streptozotocin or vehicle, to induce type 2 diabetes (T2D). All T2D and age-matched control mice were treated with or without SDF-1beta at 5 mg/kg body-weight twice a week and also continually received HFD or ND for 3 months. At the end of 6-month study, after cardiac functions were measured, mice were euthanized to collect heart tissue. For in vitro mechanistic study, H9c2 cells were exposed to palmitate to mimic in vivo condition of T2D. SDF-1beta prevented T2D-induced cardiac dysfunction and fibrosis and T2D-down-regulated KLF15 expression in wild-type diabetic heart tissue. However, the preventive effects of SDF-1beta on both KLF15 expression and fibrosis was abolished, with partial cardiac protection in Klf15-KO/T2D mice. These results demonstrate partial KLF15-dependence for SDF-1beta's cardiac fibrotic protection from T2D, but not on SDF-1beta's protective effects on T2D-induced cardiac dysfunction. Further study showed that SDF-1beta inhibited palmitate-induced cardiomyocyte fibrosis through its receptor CXCR7-mediated activation of p38beta MAPK signaling pathway. |
