Role of microRNAs in kidney homeostasis and disease

Chandrasekaran, Karthikeyan; Karolina, Dwi Setyowati; Sepramaniam, Sugunavathi; Armugam, Arunmozhiarasi; Wintour, E. M.; Bertram, John F.; Jeyaseelan, Kandiah

doi:10.1038/ki.2011.448

Cited by 191 publications

(154 citation statements)

References 188 publications

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“…The dysregulation of miRNAs results in various disease states, including renal dysfunction and injury (6)(7)(8). In recent studies, we (9-11) and others (12)(13)(14) found that miRNAs can be secreted by cells into body fluids and these circulating miRNAs are highly stable.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.Design, setting, participants, & measurements Candidate urinary miRNAs were identified in pooled urine samples from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were then validated using individual samples. Their levels were compared both under different treatment responses in a prospective study of FSGS and in patients with different membranous nephropathy (MN) and diabetic nephropathy (DN) disease activity. The prediction of these miRNAs for treatment responses was further analyzed in both retrospective and prospective cohorts of patients with FSGS.Results All 54 miRNAs were included as candidate biomarkers, including those with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array as well as those with conserved expression in kidneys and involved in immune response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80). Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with an area under the curve of $0.80. After steroid treatment, their levels were lower in steroid-responsive patients with FSGS (all P,0.001), but were unchanged in steroid-resistant patients. The levels of miRNAs were similar between active MN and MN in remission as well as active DN and incipient DN (all P.0.05). Urinary miR-30a-5p marginally predicted the response to steroid treatment in patients with FSGS-A, with an area under the curve of 0.63 (P=0.03). ConclusionsThe levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.

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Section: Introductionmentioning

confidence: 99%

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…24,25 The role of miRNAs in kidney diseases has been an area of intense investigation in the past several years. 9,[26][27][28][29][30][31][32] Work from our laboratory and other groups 9,26,[30][31][32] has elucidated the role of numerous miRNAs in the pathophysiology of DN. However, the in vivo functional roles of miRNAs in renal inflammation during DN are not clear.…”

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confidence: 99%

Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

Bhatt

Lanting

Jia

et al. 2015

JASN

159

130

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Inflammation has a critical role in the pathogenesis of diabetic complications, including diabetic nephropathy (DN). MicroRNAs have recently emerged as important regulators of DN. However, the role of microRNAs in the regulation of inflammation during DN is poorly understood. Here, we examined the in vivo role of microRNA-146a (miR-146a), a known anti-inflammatory microRNA, in the pathogenesis of DN. In a model of streptozotocin-induced diabetes, miR-146a 2/2 mice showed significantly exacerbated proteinuria, renal macrophage infiltration, glomerular hypertrophy, and fibrosis relative to the respective levels in control wild-type mice. Diabetes-induced upregulation of proinflammatory and profibrotic genes was significantly greater in the kidneys of miR-146a 2/2 than in the kidneys of wild-type mice. Notably, miR146a expression increased in both peritoneal and intrarenal macrophages in diabetic wild-type mice. Mechanistically, miR-146a deficiency during diabetes led to increased expression of M1 activation markers and suppression of M2 markers in macrophages. Concomitant with increased expression of proinflammatory cytokines, such as IL-1b and IL-18, markers of inflammasome activation also increased in the macrophages of diabetic miR-146a 2/2 mice. These studies suggest that in early DN, miR-146a upregulation exerts a protective effect by downregulating target inflammation-related genes, resulting in suppression of proinflammatory and inflammasome gene activation. Loss of this protective mechanism in miR-146a 2/2 mice leads to accelerated DN. Taken together, these results identify miR-146a as a novel anti-inflammatory noncoding RNA modulator of DN. 27: 227727: -228827: , 201627: . doi: 10.1681 Diabetic nephropathy (DN) is the leading cause of CKD and ESRD. 1-6 Development and progression of DN involve a complex interplay among metabolic, hemodynamic, growth, and inflammatory factors. 1,3,[7][8][9][10][11][12][13] The progressive decline in renal function during DN is a result of a multitude of pathologic changes in the kidneys, including glomerular and tubular hypertrophy, macrophage infiltration, extracellular matrix (ECM) accumulation in multiple renal cells, mesangial expansion, endothelial dysfunction, and podocyte injury. 1,3,[7][8][9][10][11][12][14][15][16] These pathologic changes clinically manifest as proteinuria and a steady deterioration in GFR. 3,4,16 Identification of molecular pathways that contribute to the pathophysiology of DN is imperative for the development of new therapeutic strategies. J Am Soc NephrolConversely, identification of factors that exert adaptive and protective roles in the early stages of DN can be exploited to prevent progression to ESRD.

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“…There are also emerging reports about microRNAs in renal field. Several comprehensive reviews of microRNAs research on kidney development, function, and diseases have been previously published [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. This review will focus on the current research progress of microRNAs in diabetic kidney disease.…”

Section: Micrornasmentioning

confidence: 99%

microRNAs in Diabetic Kidney Disease

Chung

2015

Advances in Experimental Medicine and Biology

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Role of microRNAs in kidney homeostasis and disease

Cited by 191 publications

References 188 publications

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

microRNAs in Diabetic Kidney Disease

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