miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6

Abstract

Renal fibrosis is associated with the reduction in the functional renal parenchyma and in most cases progresses to end-stage kidney failure, a devastating condition that requires lifelong dialysis or kidney transplantation. However, due to the extreme complexity in the pathogenesis of renal fibrosis and our limited knowledge, therapeutic options for renal fibrosis in the clinical setting are still scarce and often ineffective. Hence, further studies on the molecular mechanisms underlying renal fibrosis are compellingly needed. Multiple miRNAs have demonstrated to participate in kidney diseases in a TGF-β dependent or independent manner, but there is very little known about miR-155-5p on renal fibrosis. In the present study, we firstly explored the expression level and functions of miR-155-5p in the setting of renal fibrosis. Our research revealed that miR-155-5p is highly expressed in kidney tissues from patients and unilateral ureteral obstruction (UUO) rat models, and miR-155-5p knockdown significantly blocks renal fibrosis both in vivo and in vitro. In mechanism, our data demonstrate that miR-155-5p promotes renal fibrosis by increasing the phosphorylated activation of STAT3 via targeting SOCS1/6. Altogether, our findings highlight a miR-155-5p/SOCS/STAT3 axis in the pathogenesis of renal fibrosis, which may provide promising therapeutic targets for clinical prevention of this disease.

Molecular and functional profiling of apical versus basolateral small extracellular vesicles derived from primary human proximal tubular epithelial cells under inflammatory conditions

“…Of the 12 lipid species significantly up‐regulated in apical sEV derived from inflammatory versus normal PTEC, four ceramide species (Cer d18:1/16:0, Cer d18:1/20:0, Cer d18:1/22:0, Cer d18:1/24:0) have been previously reported as elevated in the urine of diabetic nephropathy patients and correlating with urinary biomarkers of renal tubular injury (e.g., N‐acetyl‐β‐D‐glucosaminidase; NAG) (Morita et al., 2020). Moreover, three of the 14 defined miRNA species significantly elevated in apical sEV derived from inflammatory PTEC (miR‐155‐5p, miR‐132‐3p, miR‐423‐5p) have been implicated in pathways of kidney injury (Lv et al., 2018; Yuan et al., 2017; Zhang et al., 2020). In particular, elevated urinary levels of miR‐155 have been reported in patients with diabetic nephropathy (Beltrami et al., 2018) and IgA nephropathy (Wang et al., 2011), whilst miR‐423 is increased in the urine of AKI patients (Ramachandran et al., 2013).…”

Toll-Like Receptors in Acute Kidney Injury

“…For example, miR-155-5p reduces the expression of MyD88 and causes the abrogation of NFκB activation. miR-155-5p is highly expressed in kidneys from renal patients and experimental obstructive renal models, promoting renal fibrosis [ 132 ]. However, the relationship between miR-155-5p and acute renal inflammation has not been reported and further studies are required.…”

miR-155–5p predictive role to decelerate foam cell atherosclerosis through CD36, VAV3, and SOCS1 pathway

“…Recent publications by Ye et al 2016, Chang et al 2016, Zhang et al, 2020 demonstrated that SOCS1 was the direct target of miR-155–5p by performing a luciferase reporter assay using HEK293 cells. The cells were co-transfected with the wild-type (WT) or mutated (Mut) SOCS1 luciferase reporter vector, together with miR-155 mimic and the control for 24 and 48 h. The result showed that luciferase activity was significantly inhibited in cells transfected with WT SOCS1 and miR-155 mimic, but not in cells transfected with mutation SOCS1 and miR-155 mimic [ 33 , 50 , 51 ]. Therefore, our results provide justification for further evaluation about the role of miR-155–5p in foam cell atherosclerosis by doing luciferase assay to get transcriptional activity profile of miRNA with 3′UTR of gene targets.…”