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GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney

The relationship between hydrogen sulfide (H(2)S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibros...

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Autores principales: John, AM Sashi Papu, Kundu, Sourav, Pushpakumar, Sathnur, Fordham, Maura, Weber, Gregory, Mukhopadhyay, Manas, Sen, Utpal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589897/
https://www.ncbi.nlm.nih.gov/pubmed/28883608
http://dx.doi.org/10.1038/s41598-017-11256-3
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author John, AM Sashi Papu
Kundu, Sourav
Pushpakumar, Sathnur
Fordham, Maura
Weber, Gregory
Mukhopadhyay, Manas
Sen, Utpal
author_facet John, AM Sashi Papu
Kundu, Sourav
Pushpakumar, Sathnur
Fordham, Maura
Weber, Gregory
Mukhopadhyay, Manas
Sen, Utpal
author_sort John, AM Sashi Papu
collection PubMed
description The relationship between hydrogen sulfide (H(2)S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H(2)S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H(2)S donor. In diabetic mice, plasma H(2)S levels were decreased while ROS and expression of its modulator (ROMO1) were increased. In addition, alteration of MMPs-9, −13 and −14 expression, PARP-1, HIF1α, and increased collagen biosynthesis as well as collagen cross-linking protein, P4HA1 and PLOD2 were observed along with diminished vascular density in diabetic kidney. These changes were ameliorated by GYY4137. Further, downregulated miRNA-194 was normalized by GYY4137 in diabetic kidney. Similar results were obtained in in vitro condition. Interestingly, miR-194 mimic also diminished ROS production, and normalized ROMO1, MMPs-9, −13 and −14, and PARP-1 along with collagen biosynthesis and cross-linking protein in HG condition. We conclude that decrease H(2)S diminishes miR-194, induces collagen deposition and realignment leading to fibrosis and renovascular constriction in diabetes. GYY4137 mitigates renal fibrosis in diabetes through miR-194-dependent pathway.
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spelling pubmed-55898972017-09-13 GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney John, AM Sashi Papu Kundu, Sourav Pushpakumar, Sathnur Fordham, Maura Weber, Gregory Mukhopadhyay, Manas Sen, Utpal Sci Rep Article The relationship between hydrogen sulfide (H(2)S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H(2)S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H(2)S donor. In diabetic mice, plasma H(2)S levels were decreased while ROS and expression of its modulator (ROMO1) were increased. In addition, alteration of MMPs-9, −13 and −14 expression, PARP-1, HIF1α, and increased collagen biosynthesis as well as collagen cross-linking protein, P4HA1 and PLOD2 were observed along with diminished vascular density in diabetic kidney. These changes were ameliorated by GYY4137. Further, downregulated miRNA-194 was normalized by GYY4137 in diabetic kidney. Similar results were obtained in in vitro condition. Interestingly, miR-194 mimic also diminished ROS production, and normalized ROMO1, MMPs-9, −13 and −14, and PARP-1 along with collagen biosynthesis and cross-linking protein in HG condition. We conclude that decrease H(2)S diminishes miR-194, induces collagen deposition and realignment leading to fibrosis and renovascular constriction in diabetes. GYY4137 mitigates renal fibrosis in diabetes through miR-194-dependent pathway. Nature Publishing Group UK 2017-09-07 /pmc/articles/PMC5589897/ /pubmed/28883608 http://dx.doi.org/10.1038/s41598-017-11256-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
John, AM Sashi Papu
Kundu, Sourav
Pushpakumar, Sathnur
Fordham, Maura
Weber, Gregory
Mukhopadhyay, Manas
Sen, Utpal
GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
title GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
title_full GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
title_fullStr GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
title_full_unstemmed GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
title_short GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney
title_sort gyy4137, a hydrogen sulfide donor modulates mir194-dependent collagen realignment in diabetic kidney
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589897/
https://www.ncbi.nlm.nih.gov/pubmed/28883608
http://dx.doi.org/10.1038/s41598-017-11256-3
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