N-acetyl-seryl-aspartyl-lysyl-proline Inhibits Diabetes-Associated Kidney Fibrosis and Endothelial-Mesenchymal Transition
Joint Authors
Srivastava, Swayam Prakash
Kanasaki, Keizo
Ishigaki, Yasuhito
Kitada, Munehiro
Nagai, Takako
Nakamura, Yuka
Kanasaki, Megumi
Shi, Sen
Koya, Daisuke
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-03-24
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Endothelial-to-mesenchymal transition (EndMT) emerges as an important source of fibroblasts.
MicroRNA let-7 exhibits anti-EndMT effects and fibroblast growth factor (FGF) receptor has been shown to be an important in microRNA let-7 expression.
The endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a substrate of angiotensin-converting enzyme (ACE).
Here, we found that AcSDKP inhibited the EndMT and exhibited fibrotic effects that were associated with FGF receptor-mediated anti-fibrotic program.
Conventional ACE inhibitor plus AcSDKP ameliorated kidney fibrosis and inhibited EndMT compared to therapy with the ACE inhibitor alone in diabetic CD-1 mice.
The endogenous AcSDKP levels were suppressed in diabetic animals.
Cytokines induced cultured endothelial cells into EndMT; coincubation with AcSDKP inhibited EndMT.
Expression of microRNA let-7 family was suppressed in the diabetic kidney; antifibrotic and anti-EndMT effects of AcSDKP were associated with the restoration of microRNA let-7 levels.
AcSDKP restored diabetes- or cytokines-suppressed FGF receptor expression/phosphorylation into normal levels both in vivo and in vitro.
These results suggest that AcSDKP is an endogenous antifibrotic molecule that has the potential to cure diabetic kidney fibrosis via an inhibition of the EndMT associated with the restoration of FGF receptor and microRNA let-7.
American Psychological Association (APA)
Nagai, Takako& Kanasaki, Megumi& Srivastava, Swayam Prakash& Nakamura, Yuka& Ishigaki, Yasuhito& Kitada, Munehiro…[et al.]. 2014. N-acetyl-seryl-aspartyl-lysyl-proline Inhibits Diabetes-Associated Kidney Fibrosis and Endothelial-Mesenchymal Transition. BioMed Research International،Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-491361
Modern Language Association (MLA)
Nagai, Takako…[et al.]. N-acetyl-seryl-aspartyl-lysyl-proline Inhibits Diabetes-Associated Kidney Fibrosis and Endothelial-Mesenchymal Transition. BioMed Research International No. 2014 (2014), pp.1-12.
https://search.emarefa.net/detail/BIM-491361
American Medical Association (AMA)
Nagai, Takako& Kanasaki, Megumi& Srivastava, Swayam Prakash& Nakamura, Yuka& Ishigaki, Yasuhito& Kitada, Munehiro…[et al.]. N-acetyl-seryl-aspartyl-lysyl-proline Inhibits Diabetes-Associated Kidney Fibrosis and Endothelial-Mesenchymal Transition. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-491361
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-491361