Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs

Autor: Julie E. Goodwin, Daisuke Koya, Keizo Kanasaki, Swayam Prakash Srivastava
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
kidney fibrosis
Angiotensin-Converting Enzyme Inhibitors
Stimulation
Angiotensin II Receptor Blockers
Pharmacology
urologic and male genital diseases
Diabetic nephropathy
Mice
0302 clinical medicine
DPP-4
Transforming Growth Factor beta
EndMT
Medicine
Diabetic Nephropathies
AcSDKP
Genetics (clinical)
diabetic nephropathy
ACE
ARBs
EMT
chemistry.chemical_classification
biology
Drug Synergism
3. Good health
030220 oncology & carcinogenesis
Oligopeptides
Signal Transduction
lcsh:QH426-470
Dipeptidyl Peptidase 4
Article
Cell Line
Diabetes Mellitus
Experimental
Angiotensin Receptor Antagonists
03 medical and health sciences
microRNA
Genetics
Renal fibrosis
Animals
Humans
cardiovascular diseases
Dipeptidyl peptidase-4
business.industry
Angiotensin-converting enzyme
medicine.disease
Disease Models
Animal
MicroRNAs
lcsh:Genetics
030104 developmental biology
Enzyme
Gene Expression Regulation
chemistry
biology.protein
business
Zdroj: Genes
Volume 11
Issue 2
Genes, Vol 11, Iss 2, p 211 (2020)
ISSN: 2073-4425
DOI: 10.3390/genes11020211
Popis: Two class of drugs 1) angiotensin-converting enzyme inhibitors (ACEis) and 2) angiotensin II receptor blockers (ARBs) are well-known conventional drugs that can retard the progression of chronic nephropathies to end-stage renal disease. However, there is a lack of comparative studies on the effects of ACEi versus ARB on renal fibrosis. Here, we observed that ACEi ameliorated renal fibrosis by mitigating DPP-4 and TGF&beta
signaling, whereas, ARB did not show. Moreover, the combination of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), one of the substrates of ACE, with ACEi slightly enhanced the inhibitory effects of ACEi on DPP-4 and associated-TGF&beta
signaling. Further, the comprehensive miRome analysis in kidneys of ACEi+AcSDKP (combination) treatment revealed the emergence of miR-29s and miR-let-7s as key antifibrotic players. Treatment of cultured cells with ACEi alone or in combination with AcSDKP prevented the downregulated expression of miR-29s and miR-let-7s induced by TGF&beta
stimulation. Interestingly, ACEi also restored miR-29 and miR-let-7 family cross-talk in endothelial cells, an effect that is shared by AcSDKP suggesting that AcSDKP may be partially involved in the anti-mesenchymal action of ACEi. The results of the present study promise to advance our understanding of how ACEi regulates antifibrotic microRNAs crosstalk and DPP-4 associated-fibrogenic processes which is a critical event in the development of diabetic kidney disease.
Databáze: OpenAIRE
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