miR-29b attenuates histone deacetylase-4 mediated podocyte dysfunction and renal fibrosis in diabetic nephropathy.
Diabetic nephropathy
HDAC4
Histone modifications
Renal fibrosis
TGF-β1
miR-29b
Journal
Journal of diabetes and metabolic disorders
ISSN: 2251-6581
Titre abrégé: J Diabetes Metab Disord
Pays: Switzerland
ID NLM: 101590741
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
21
06
2019
accepted:
05
11
2019
entrez:
19
6
2020
pubmed:
19
6
2020
medline:
19
6
2020
Statut:
epublish
Résumé
As epigenetic modifications like chromatin histone modifications have been suggested to play a role in the pathophysiology of Diabetic Nephropathy (DN) and are also found to be regulated by microRNAs. Our main purpose was to explore the role of microRNA in histone modulations associated with DN. There is downregulation of miR-29b due to advanced glycation end products in diabetes. Histone Deacetylase-4 (HDAC4) is amongst the histone modulators which promotes podocytes' impairment and upregulates transforming growth factor-1 (TGF-β1) leading to renal fibrosis. Moreover, macrophage infiltration causes podocytes' apoptosis and IL-6 mediated inflammation. As miR-29b is downregulated in diabetes and HDAC4, TGF-β1 and IL-6 could be the possible therapeutic targets in DN, our study was focussed on unveiling the role of miR-29b in modulation of HDAC4 and hence, in podocyte dysfunction and renal fibrosis in DN. In silico analysis and luciferase assay were done to study the interaction between miR-29b and HDAC4. In-vitro DN model was developed in podocytes and miR-29b mimics were transfected It was found that miR-29b targets the 3' untranslated region of HDAC4. In both in-vitro and in-vivo DN model, downregulation of miR-29b and subsequent increase in HDAC4 expression was observed. The miR-29b mimics suppressed podocytes' inflammation mediated through macrophages and attenuated HDAC4 expression, glomerular damage and renal fibrosis. This study concludes that miR-29b regulates the expression of HDAC4 which plays a role in controlling renal fibrosis and podocytes' impairment in DN.
Identifiants
pubmed: 32550152
doi: 10.1007/s40200-019-00469-0
pii: 469
pmc: PMC7270417
doi:
Types de publication
Journal Article
Langues
eng
Pagination
13-27Informations de copyright
© Springer Nature Switzerland AG 2019.
Déclaration de conflit d'intérêts
Conflict of interestThe authors declare that they have no conflict of interest.
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