دورية أكاديمية
A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease
| العنوان: | A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease |
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| المؤلفون: | Prieto, Ignacio, Kavanagh, María, Jiménez Castilla, Luna, Pardines, Marisa, Herrero del Real, Isabel, Flores Muñoz, Monica, Egido, Jesus, López Franco, Óscar, Gómez Guerrero, Carmen |
| المساهمون: | UAM. Departamento de Medicina |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2024 |
| المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| مصطلحات موضوعية: | © 2023 The Author(s), Medicina |
| الوصف: | 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 ; This research was funded by grants from Spanish Ministry of Science and Innovation (RTI2018-098788-B-I00 and PID2021-127741OBI00) to C.G.-G., Instituto de Salud Carlos III (PI20/00487) to J.E, CIBERDEM (postdoctoral contract) to I.P., and Conacyt-Mexico (CB-2015-01 256639 and FOP02-2022-02 321869) to O.L.-F. The authors thank Ana Melgar and Patricia Saperas (IIS-FJD, Madrid) for technical support in mouse sample processing and histology, and Carmen Liliana Peña ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Molecular Therapy Nucleic Acids; https://doi.org/10.1016/j.omtn.2023.102041Test; Gobierno de España. RTI2018-098788-B-I00; Gobierno de España. PID2021-127741OBI00; Molecular Therapy Nucleic Acids 34 (2023): 102041; 2162-2531 (online); http://hdl.handle.net/10486/709648Test; 102041-1; 102041; 34 |
| DOI: | 10.1016/j.omtn.2023.102041 |
| الإتاحة: | https://doi.org/10.1016/j.omtn.2023.102041Test http://hdl.handle.net/10486/709648Test |
| حقوق: | © 2023 The Author(s) ; Reconocimiento – NoComercial – SinObraDerivada ; openAccess |
| رقم الانضمام: | edsbas.F4E9147 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.omtn.2023.102041 |
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