Mir-138 plays an important role in diabetic nephropathy through SIRT1-p38-TTP regulatory axis

Abstract

Background : Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and is one of the most common and serious complications of diabetes mellitus (DM). SIRT1 and TTP are two important protective factors in DN, however, the regulatory relationship between SIRT1 and TTP and the underneath mechanism are interesting but still unclear. Identifying the key factors that regulate SIRT1 or TTP may be of great value to the understanding and treatment of the DN. Methods : in this study, through systematic experimental methods, we found that the expression of miR-138 was significantly up-regulated in DN clinical patients samples, and our experimental results suggested that miR-138 could bind the 3’UTR of SIRT1 and inhibit its expression in both cultured podocytes and db/db mice kidney tissues. Results : furthermore, our in vitro and in vivo date also indicated miR-138 could target SIRT1 and affect TTP through p38 pathway. And down-regulation of miR-138 attenuated podocyte injury and showed some extend of therapeutic effects in DN mice models. Conclusion : our findings reveal that the regulatory axis of miR-138-SIRT1-p38-TTP might play a key role in DN. We believe these findings may be of some value for deepening the understanding of DN and may serve as a reference for future treatment of this disease.

Post-transcriptional control by RNA-binding proteins in diabetes and its related complications

“…Moreover, glucose in high concentration could upregulate miR-138 level and repress the expression of SIRT1 by binding to its 3′UTR, resulting in the TTP inhibition in cultured podocytes as well as db/db mice renal tissues. Lower TTP expression causes an increase in the expression of inflammatory factors, leaving podocytes in an inflammatory state for an extended period of time, which leads to loss of normal morphology and function (Liu et al, 2021). RBP IGFBP-1 expression is reduced and affects the function of podocytes via β1-integrin/FAK signaling in human type 2 diabetic glomeruli (Lay et al, 2021).…”

Plasma Lnc-UCA1/miR-138 axis as a potential biomarker for gestational diabetes mellitus and neonatal prognosis

“…Long noncoding RNA urothelial carcinoma-associated 1 (Lnc-UCA1), locating on chromosome 14q13.12 region and encoding 3 isoforms, is found to be implicated in various diseases, especially metabolic diseases [13][14][15][16]. As a direct target of Lnc-UCA1, miR-138 is also closely related to pathogenesis of type 2 diabetes mellitus [17], diabetic nephropathy [19], and GDM [20]. However, the role of Lnc-UCA1/miR-138 axis in GDM remains unknown.…”