Altered expression of microRNA miR-146a correlates with the development of chronic renal inflammation

Ichii, Osamu; Otsuka, Saori; Sasaki, Nobuya; Namiki, Yuka; Hashimoto, Yoshiharu; Kon, Yasuhiro

doi:10.1038/ki.2011.345

Cited by 113 publications

(99 citation statements)

References 31 publications

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“…It has been revealed that the expression of miR-146a involves in several pathological pathways including tubular atrophy and interstitial fibrosis by infiltrating inflammatory cells such as macrophage and T cell as well as with secretion of some cytokines such as IL-1β, IL-10, and CXCL leading progressive renal inflammation (25). Similar to our study, some authors demonstrated the role of miR146a in LN pathogenesis (24). In a study by Lu et al, miR-146a is not overexpressed in LN tubulointerstitial tissue, however effectively up-regulate in glomerular tissue (24).…”

Section: Discussionsupporting

confidence: 80%

“…Similar to our study, some authors demonstrated the role of miR146a in LN pathogenesis (24). In a study by Lu et al, miR-146a is not overexpressed in LN tubulointerstitial tissue, however effectively up-regulate in glomerular tissue (24). In another study, expression of miR-146a was shown to be involved in level of inflammation and thus can determine histological activity index (25).…”

Section: Discussionsupporting

confidence: 74%

“…Pathophysiological studies could demonstrate increased expression of miR-638 in both glomerular and tubuleinterstitial tissues that is directly associated with proteinuria and thus with SLE disease activity index. However, it remains uncertain whether inhibition of this miRNAs may introduce as a target therapeutic approach in LN patients (24). More evidences are available in involvement of miR146a in pathogenesis of LN, however we could not demonstrate its role in pathogenesis of disease.…”

Section: Discussioncontrasting

confidence: 44%

See 2 more Smart Citations

Assessment of microRNA profile of kidney biopsies of patients with lupus nephritis

Malakoutian¹,

Hajian²,

Ebrahimi³

et al. 2017

J Nephropathol

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Background: The changes in some epigenetic elements such as microRNAs result in aberrant immune responses leading to production and secretion of nephritogenic autoantibodies as the main fundament of lupus nephritis (LN).Objectives: The present study aimed to assess the miRNA profile of kidney biopsies in patients with LN with the purpose of describing the critical role of these elements in LN creation. Patients and Methods:In this case-control single center study 11 patients who suffered LN (as the case group) and 11 patients with normal kidney function who were candidate for nephrectomy due to cancer or cyst (as the control group) were included. Kidney biopsies were taken from all LN and control subjects. RNA was extracted and converted to cDNA, then the cDNA was evaluated using NANODROP and then intra-renal expression of candidate miRNAs were quantified in the two groups. In the present study, four topranked miRNAs, miR-638, miR-146a, miR-198, and miR-731 were selected for qRT-PCR. Results: Consistent with the microarray data, we found no significant difference in the expression of all miRNAs between LN and control groups. Using REST 2009 software, we did not also reveal any difference in expression of four miRNAs studied between the patients with LN and those without LN in both parametric and nonparametric patterns. Conclusions:The expression of miR-638, miR-146a, miR-198, and miR-731 may not be related to occurrence of LN in Iranian population.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 74%

Section: Discussioncontrasting

confidence: 44%

See 1 more Smart Citation

Assessment of microRNA profile of kidney biopsies of patients with lupus nephritis

Malakoutian¹,

Hajian²,

Ebrahimi³

et al. 2017

J Nephropathol

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“…49,[53][54][55] While some studies have shown lower miR-146a expression during DN, 49 others have shown higher expression. 53,54 Our results (Figures 1, 2, and 7) show a significant upregulation of miR-146a in the peritoneal macrophages as well as in the kidneys of STZ-induced diabetic mouse models.…”

Section: Discussionmentioning

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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“…Potential mechanism for such association might be due to impaired ability to inhibit apoptosis and inflammation among GG homozygotes compared with AA homozygotes. miR-146a plays important roles in regulating the innate immunity and inflammatory responses (Rusca and Monticelli 2011;Ichii et al 2012). Aberrant expression of miR-146a has been observed in a variety of disease, including cancer, autoimmune and inflammatory diseases, and infectious diseases (Li et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Association of microRNA Polymorphisms with the Risk of Myocardial Infarction in a Chinese Population

Chen

Hong

Chen

et al. 2014

Tohoku J. Exp. Med.

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MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, such as inflammation. Dysregulation of miRNAs have been implicated in many human disease, including cardiovascular diseases. Polymorphisms in miRNA genes may affect the miRNA biogenesis and function, and thus cause changes in the expression of thousands of genes. The aim of this study was to examine whether miRNA polymorphisms (miR-146a rs2910164, miR-149 rs71428439, miR-196a2 rs11614913, miR-218 rs11134527, and miR-499 rs3746444) contribute to the risk for the development of myocardial infarction (MI). Five miRNA polymorphisms were genotyped in a total of 1808 subjects composed of 919 MI patients and 889 control individuals. The GG genotype of rs3746444 was found to be associated with a significantly increased risk of MI (recessive model, adjusted OR = 1.710, 95% CI: 1.058-2.763, P = 0.029). Although the CC genotype of rs2910164 significantly increased the risk of MI under dominant and additive models (P < 0.05), this difference disappeared after adjustment for age, sex, blood pressure, triglycerides, total cholesterol, HDL, LDL and diabetes. In addition, when rs3746444 and rs2910164 were evaluated together by the number of putative high-risk alleles, we found an increased risk of MI for subjects carrying 3-4 risk alleles (3-4 risk alleles vs. 0-1 risk allele, adjusted OR = 1.580, 95% CI: 1.069-2336, P = 0.022; 3-4 risk alleles vs. 0-2 risk allele, adjusted OR = 1.513, 95% CI: 1.031-2.219, P = 0.034). These findings indicate that miR-499 rs3746444 and miR-146a rs2910164 may represent novel markers of MI susceptibility.

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Altered expression of microRNA miR-146a correlates with the development of chronic renal inflammation

Cited by 113 publications

References 31 publications

Assessment of microRNA profile of kidney biopsies of patients with lupus nephritis

Assessment of microRNA profile of kidney biopsies of patients with lupus nephritis

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

Association of microRNA Polymorphisms with the Risk of Myocardial Infarction in a Chinese Population

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