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Hydrogen sulfide induces miR194 in diabetic nephropathy and mitigates renal fibrosis (689.10)
Author(s) -
Kundu Sourav,
Narayanan Nithya,
Pushpakumar Sathnur,
Sen Utpal
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.689.10
Subject(s) - diabetic nephropathy , fibrosis , diabetes mellitus , medicine , nephropathy , endocrinology , reactive oxygen species , kidney , cancer research , chemistry , biochemistry
Recent evidences suggest that hydrogen sulfide (H2S) has a therapeutic potential for several clinical complications including renovascular fibrosis. Similarly, micro RNAs (miRs) has also gained substantial biomedical research interest with relevance to renal fibrosis. In this regard miRs control reactive oxygen species (ROS) and high level of ROS persuades poly‐ADP‐ribose‐polymerase‐1 (PARP1) which induces extracellular matrix (ECM) associated with vascular fibrosis. Among miRs, miR194 is prevalent in the mammalian kidney; however, its role in diabetic nephropathy and whether H2S has any potential implication on miRs regulation associated with diabetic renal fibrosis is unknown. Hypothesis: The objective of this study was to determine whether miR194 has potential roles in diabetic nephropathy which leads to PARP 1 activation by ROS induction causing renal fibrosis. Materials and methods: C57BL/6J (Wild type, WT) and diabetic (Akita, C57BL/6J‐Ins2Akita) mice were used in this study. Animals were treated without or with 0.05 g/L of NaHS in drinking water for 4 weeks. In vitro studies were performed using mouse glomerular endothelial cells (MGECs). Results: Expression of miR‐194 was significantly decreased in Akita animals compared to control as revealed by real time PCR. Increased expression of miR194 has been observed following H2S treatment. In diabetic animals increased ROS and PARP1 levels were measured. Levels of matricellular proteins as well as genes, responsible for collagen re‐alignment, showed higher expression in diabetes and significantly reduced following H2S treatment. We conclude that decrease in miR194 in diabetes contributes to increased expression of ECM components in renal fibrosis and treatment with H2S ameliorates these effects. Grant Funding Source : HL‐104103