Match!

Lin28a protects against cardiac ischaemia/reperfusion injury in diabetic mice through the insulin‐PI3K‐mTOR pathway

Published on Jun 1, 2015in Journal of Cellular and Molecular Medicine
· DOI :10.1111/jcmm.12369
Mingming Zhang12
Estimated H-index: 12
(Fourth Military Medical University),
Dongdong Sun19
Estimated H-index: 19
(Fourth Military Medical University)
+ 7 AuthorsHaichang Wang34
Estimated H-index: 34
(Fourth Military Medical University)
Abstract
The insulin-PI3K-mTOR pathway exhibits a variety of cardiovascular activities including protection against I/R injury. Lin28a enhanced glucose uptake and insulin-sensitivity via insulin-PI3K-mTOR signalling pathway. However, the role of lin28a on experimental cardiac I/R injury in diabetic mice are not well understood. Diabetic mice underwent 30 min. of ischaemia followed by 3 hrs of reperfusion. Animals were randomized to be treated with lentivirus carrying lin28a siRNA (siLin28a) or lin28a cDNA (Lin28a) 72 hrs before coronary artery ligation. Myocardial infarct size (IS), cardiac function, cardiomyocyte apoptosis and mitochondria morphology in diabetic mice who underwent cardiac I/R injury were compared between groups. The target proteins of lin28a were examined by western blot analysis. Lin28a overexpression significantly reduced myocardial IS, improved LV ejection fraction (LVEF), decreased myocardial apoptotic index and alleviated mitochondria cristae destruction in diabetic mice underwent cardiac I/R injury. Lin28a knockdown exacerbated cardiac I/R injury as demonstrated by increased IS, decreased LVEF, increased apoptotic index and aggravated mitochondria cristae destruction. Interestingly, pre-treatment with rapamycin abolished the beneficial effects of lin28a overexpression. Lin28a overexpression increased, while Lin28a knockdown decreased the expression of IGF1R, p-Akt, p-mTOR and p-p70s6k after cardiac I/R injury in diabetic mice. Rapamycin pre-treatment abolished the effects of increased p-mTOR and p-p70s6k expression exerted by lin28a overexpression. This study indicates that lin28a overexpression reduces IS, improves cardiac function, decreases cardiomyocyte apoptosis index and alleviates cardiomyocyte mitochondria impairment after cardiac I/R injury in diabetic mice. The mechanism responsible for the effects of lin28a is associated with the insulin-PI3K-mTOR dependent pathway.
  • References (28)
  • Citations (16)
References28
Newest
#1Jonas M. Kristensen (UCPH: University of Copenhagen)H-Index: 12
#2Vibe Skov (OUH: Odense University Hospital)H-Index: 10
Last.Kurt Højlund (UCPH: University of Copenhagen)H-Index: 43
view all 7 authors...
#1Owen L. Woodman (RMIT: RMIT University)H-Index: 28
#2R. Long (French Institute of Health and Medical Research)H-Index: 1
Last.D. Morin (French Institute of Health and Medical Research)H-Index: 1
view all 6 authors...
#1Gen Shinoda (Harvard University)H-Index: 7
#2Ng Shyh-Chang (Harvard University)H-Index: 22
Last.George Q. Daley (Harvard University)H-Index: 108
view all 14 authors...
#1Dongdong Sun (Fourth Military Medical University)H-Index: 19
#2Jie HuangH-Index: 1
Last.Haichang Wang (Fourth Military Medical University)H-Index: 34
view all 8 authors...
#1Hao ZhuH-Index: 23
#2Ng Shyh-Chang (Harvard University)H-Index: 22
Last.George Q. DaleyH-Index: 108
view all 16 authors...
Cited By16
Newest
#1Peng-Hua You (Fourth Military Medical University)H-Index: 1
#2Zheng Cheng (Fourth Military Medical University)
Last.Gong ChengH-Index: 1
view all 7 authors...
#1Liping Wei (NKU: Nankai University)H-Index: 1
#2Xuseng Sun (Tianjin Medical University)H-Index: 1
Last.Yue Xu (Tianjin University of Traditional Chinese Medicine)H-Index: 1
view all 6 authors...
#1Arun Samidurai (VCU: Virginia Commonwealth University)H-Index: 8
#2Rakesh C. Kukreja (VCU: Virginia Commonwealth University)H-Index: 58
Last.Anindita Das (VCU: Virginia Commonwealth University)H-Index: 33
view all 3 authors...
#1Haibo Chen (Peking Union Medical College)H-Index: 1
#2Si Liu (Peking Union Medical College)H-Index: 2
Last.Xi Chen (Peking Union Medical College)H-Index: 14
view all 7 authors...
#1Chen Lin (Fourth Military Medical University)H-Index: 1
#2Mingming Zhang (Fourth Military Medical University)H-Index: 12
Last.Wenyi Guo (Fourth Military Medical University)H-Index: 13
view all 13 authors...
#1Robin Verjans (UM: Maastricht University)H-Index: 3
#2Marc van Bilsen (UM: Maastricht University)H-Index: 35
Last.Blanche Schroen (UM: Maastricht University)H-Index: 26
view all 3 authors...
View next paperLin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway.