首页|KLF15 negatively regulates cardiac fibrosis by which SDF-1 beta attenuates cardiac fibrosis in type 2 diabetic mice

KLF15 negatively regulates cardiac fibrosis by which SDF-1 beta attenuates cardiac fibrosis in type 2 diabetic mice

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  • NSTL
  • Elsevier
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-1 beta 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-1 beta 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-1 beta 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-1 beta's cardiac fibrotic protection from T2D, but not on SDF-1 beta' s protective effects on T2D-induced cardiac dysfunction. Further study showed that SDF-1 beta inhibited palmitate-induced cardiomyocyte fibrosis through its receptor CXCR7-mediated activation of p38 beta MAPK signaling pathway.

Type 2 diabetesDiabetic cardiomyopathyKLF15SDF-1 betaCardiac fibrosis

Rane, Madhavi、Zhao, Yuguang、Tian, Yuanyuan、Wang, Zhenyu、Zheng, Xiangyu、Song, Wenjing、Cai, Lu

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Univ Louisville, Dept Med, Div Nephrol, Sch Med, Louisville, KY 40292 USA

First Hosp Jilin Univ, Canc Ctr, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China

First Hosp Jilin Univ, Dept Spinal Surg, Changchun 130021, Jilin, Peoples R China

First Hosp Jilin Univ, Dept Neurol, Changchun 130021, Jilin, Peoples R China

Univ Louisville, Pediat Res Inst, Dept Pediat, Sch Med, Louisville, KY 40292 USA

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2021

10.1016/j.taap.2021.115654

Toxicology and Applied Pharmacology

Toxicology and Applied Pharmacology

SCI
ISSN：0041-008X
年,卷(期)：2021.427
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