A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123002597 |
| _version_ | 1797660290552168448 |
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| author | Ignacio Prieto María Kavanagh Luna Jimenez-Castilla Marisa Pardines Iolanda Lazaro Isabel Herrero del Real Monica Flores-Muñoz Jesus Egido Oscar Lopez-Franco Carmen Gomez-Guerrero |
| author_facet | Ignacio Prieto María Kavanagh Luna Jimenez-Castilla Marisa Pardines Iolanda Lazaro Isabel Herrero del Real Monica Flores-Muñoz Jesus Egido Oscar Lopez-Franco Carmen Gomez-Guerrero |
| author_sort | Ignacio Prieto |
| collection | DOAJ |
| description | Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were conducted to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of the JAK/STAT pathway during renal inflammation and DKD. In experimental models of mesangial injury and diabetes, miR-155-5p expression correlated inversely with SOCS1 and positively with albuminuria and expression levels of cytokines and prooxidant genes. In renal cells, miR-155-5p mimic downregulated SOCS1 and promoted STAT1/3 activation, cytokine expression, and cell proliferation and migration. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammation and hyperglycemia damage. In vivo, SOCS1 gene delivery decreased miR-155-5p and kidney injury in diabetic mice. Moreover, therapeutic inhibition of miR-155-5p suppressed STAT1/3 activation and alleviated albuminuria, mesangial damage, and renal expression of inflammatory and fibrotic genes. In conclusion, modulation of the miR-155/SOCS1 axis protects kidneys against diabetic damage, thus highlighting its potential as therapeutic target for DKD. |
| first_indexed | 2024-03-11T18:28:39Z |
| format | Article |
| id | doaj.art-22cf8225344640efab8c0fb9c322b23f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-03-11T18:28:39Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-22cf8225344640efab8c0fb9c322b23f2023-10-13T13:53:22ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-12-0134102041A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney diseaseIgnacio Prieto0María Kavanagh1Luna Jimenez-Castilla2Marisa Pardines3Iolanda Lazaro4Isabel Herrero del Real5Monica Flores-Muñoz6Jesus Egido7Oscar Lopez-Franco8Carmen Gomez-Guerrero9Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, SpainRenal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, SpainRenal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, SpainRenal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, SpainCardiovascular Risk and Nutrition, Hospital del Mar Medical Research Institute-IMIM, 08003 Barcelona, SpainRenal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, SpainTranslational Medicine Lab, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa 91140, Veracruz, MexicoRenal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, SpainTranslational Medicine Lab, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa 91140, Veracruz, Mexico; Corresponding author: OscarLopez-Franco, Translational Medicine Lab, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa, Veracruz 91140, Mexico.Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain; Corresponding author: Carmen Gomez-Guerrero, Renal, Vascular and Diabetes Research Lab, IIS-FJD/UAM, Avda Reyes Catolicos 2, 28040 Madrid, Spain.Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were conducted to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of the JAK/STAT pathway during renal inflammation and DKD. In experimental models of mesangial injury and diabetes, miR-155-5p expression correlated inversely with SOCS1 and positively with albuminuria and expression levels of cytokines and prooxidant genes. In renal cells, miR-155-5p mimic downregulated SOCS1 and promoted STAT1/3 activation, cytokine expression, and cell proliferation and migration. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammation and hyperglycemia damage. In vivo, SOCS1 gene delivery decreased miR-155-5p and kidney injury in diabetic mice. Moreover, therapeutic inhibition of miR-155-5p suppressed STAT1/3 activation and alleviated albuminuria, mesangial damage, and renal expression of inflammatory and fibrotic genes. In conclusion, modulation of the miR-155/SOCS1 axis protects kidneys against diabetic damage, thus highlighting its potential as therapeutic target for DKD.http://www.sciencedirect.com/science/article/pii/S2162253123002597MT: Non-coding RNAs: diabetesrenal inflammationdiabetic kidney diseasefibrosismicroRNAsignal transduction |
| spellingShingle | Ignacio Prieto María Kavanagh Luna Jimenez-Castilla Marisa Pardines Iolanda Lazaro Isabel Herrero del Real Monica Flores-Muñoz Jesus Egido Oscar Lopez-Franco Carmen Gomez-Guerrero A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease Molecular Therapy: Nucleic Acids MT: Non-coding RNAs: diabetes renal inflammation diabetic kidney disease fibrosis microRNA signal transduction |
| title | A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease |
| title_full | A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease |
| title_fullStr | A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease |
| title_full_unstemmed | A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease |
| title_short | A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease |
| title_sort | mutual regulatory loop between mir 155 and socs1 influences renal inflammation and diabetic kidney disease |
| topic | MT: Non-coding RNAs: diabetes renal inflammation diabetic kidney disease fibrosis microRNA signal transduction |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123002597 |
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