A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease

Prieto, IgnacioKavanagh, MaríaJiménez Castilla, LunaPardines, MarisaLázaro, IolandaHerrero del Real, IsabelFlores Muñoz, MónicaEgido, Jesús (Egido de los Ríos)López Franco, ÓscarGómez Guerrero, Carmen2024-05-282024-05-282023Prieto I, Kavanagh M, Jimenez-Castilla L, Pardines M, Lazaro I, Herrero Del Real I, et al. A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease. Mol Ther Nucleic Acids. 2023 Sep 27;34:102041. DOI: 10.1016/j.omtn.2023.1020412162-2531http://hdl.handle.net/10230/60260Diabetic 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.application/pdfeng© 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney diseaseinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.omtn.2023.102041JAK/STAT/SOCSMT: Non-coding RNAsDiabetesCytokinesDiabetic kidney diseaseFibrosisHyperglycemiamicroRNARenal inflammationSignal transductioninfo:eu-repo/semantics/openAccess