Possible involvement of microRNAs in vascular damage in experimental chronic kidney disease

Taïbi, Fatiha; Metzinger, Laurent; M'Baya-Moutoula, Eléonore; Djelouat, Mohamed seif el Islam; Louvet, Loı̈c; Bugnicourt, Jean‐Marc; Poirot, Sabrina; Bengrine, Abderrahmane; Chillon, Jean‐Marc; Massy, Ziad A.

doi:10.1016/j.bbadis.2013.10.005

Cited by 72 publications

(71 citation statements)

References 39 publications

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“…miRNA levels have been associated with CKD in previous studies by our team and by other authors, in both cellular and animal models [8–10]. In a murine CKD model, we have shown that miR-126, miR-143, miR-145 and miR-223 are implicated in the vascular complications that occur during the later stages of CKD [9]. miR-126 is endothelial-specific and implicated in endothelial dysfunction [11].…”

Section: Introductionmentioning

confidence: 77%

Serum microRNAs are altered in various stages of chronic kidney disease: a preliminary study

et al. 2016

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BackgroundMicroRNAs (miRNAs) are innovative and informative blood-based biomarkers involved in numerous pathophysiological processes. In this study and based on our previous experimental data, we investigated miR-126, miR-143, miR-145, miR-155 and miR-223 as potential circulating biomarkers for the diagnosis and prognosis of patients with chronic kidney disease (CKD). The primary objective of this study was to assess the levels of miRNA expression at various stages of CKD.MethodsRNA was extracted from serum, and RT-qPCR was performed for the five miRNAs and cel-miR-39 (internal control).ResultsSerum levels of miR-143, -145 and -223 were elevated in patients with CKD compared with healthy controls. They were further increased in chronic haemodialysis patients, but were below control levels in renal transplant recipients. In contrast, circulating levels of miR-126 and miR-155 levels, which were also elevated in CKD patients, were lower in the haemodialysis group and even lower in the transplant group. Four of the five miRNA species were correlated with estimated glomerular filtration rate, and three were correlated with circulating uraemic toxins.ConclusionsThis exploratory study suggests that specific miRNAs could be biomarkers for complications of CKD, justifying further studies to link changes of miRNA levels with outcomes in CKD patients.

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Section: Introductionmentioning

confidence: 77%

Serum microRNAs are altered in various stages of chronic kidney disease: a preliminary study

et al. 2016

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“…We examined a series of miRs implicated in kidney cell apoptosis and angiogenesis. [19][20][21] Unlike the involvements of miR-21, miR-27, miR-126, and miR-192 in other forms of kidney disease, 22,23 we found no change in the expression of these miRs in RVD, possibly because of different disease and species settings. For example, miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice 24 but plays a pathogenic role in kidney fibrosis in mice with unilateral ureteral obstruction.…”

Section: Discussioncontrasting

confidence: 65%

Renal Vein Levels of MicroRNA-26a Are Lower in the Poststenotic Kidney

Zhu

Ebrahimi

Eirin

et al. 2015

Journal of the American Society of Nephrology

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MicroRNA-26a (miR-26a) is a post-transcriptional regulator that inhibits cellular differentiation and apoptosis. Renal vascular disease (RVD) induces ischemic injury characterized by tubular cell apoptosis and interstitial fibrosis. We hypothesized that miR-26a levels are reduced in the poststenotic kidney and that kidney repair achieved by adipose tissue-derived mesenchymal stem cells (ad-MSCs) is associated with restored miR-26a levels. Renal function and renal miR-26a levels were assessed in pigs with RVD not treated (n=7) or 4 weeks after intrarenal infusion of ad-MSC (2.5310 5 cells/kg; n=6), patients with RVD (n=12) or essential hypertension (n=12), and healthy volunteers (n=12). In addition, the direct effect of miR-26a on apoptosis was evaluated in a renal tubular cell culture. Compared with healthy control kidneys, swine and human poststenotic kidneys had 45.564.3% and 90.063.5% lower levels of miR-26a, respectively, which in pigs, localized to the proximal tubules. In pigs, ad-MSC delivery restored tubular miR-26a expression, attenuated tubular apoptosis and interstitial fibrosis, and improved renal function and tubular oxygen-dependent function. In vitro, miR-26a inhibition induced proximal tubular cell apoptosis and upregulated proapoptotic protein expression, which were both rescued by ad-MSC. In conclusion, decreased tubular miR-26a expression in the poststenotic kidney may be responsible for tubular cell apoptosis and renal dysfunction but can be restored using ad-MSC. Therefore, miR-26a might be a novel therapeutic target in renovascular disease.

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“…[44]. Although no study has yet measured miR-135a expression in this population, some studies have revealed the involvement of miRs in vascular damage in experimental chronic kidney disease [45], such as miR-126, -143 and -223. As miR-135a plays an important role in vascular calcification, the relationship between it and the chronic kidney disease requires further study.…”

Section: Discussionmentioning

confidence: 99%

miR-135a Suppresses Calcification in Senescent VSMCs by Regulating KLF4/STAT3 Pathway

Lin¹,

He²,

Xi³

et al. 2016

CVP

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Cellular function phenotype is regulated by various microRNAs (miRs), including miR-135a. However, how miR-135a is involved in the calcification in senescent vascular smooth muscle cells (VSMCs) is not clear yet. In the present study, we first identified the significantly altered miRNAs in VSMCs, then performed consecutive passage culture of VSMCs and analyzed the expression of miR-135a and calcification genes in the senescent phase. Next, the effects of the miR-135a inhibition on calcification and calcification genes were analyzed. The luciferase assay was used to validate the target protein of miR-135a. The western blotting was used to determine the effects of miR-135a on Krüppel-like factor 4 (KLF4) and signal transducer and activator of transcription 3 protein (STAT3) expression, as well as the relationship between KLF4 and STAT3. Finally, the quantified cellular calcification was measured to examine the involvement of miR-135a, KLF4 and STAT3 in VSMCs calcification. Our results showed that miR-135a was significantly altered in VSMCs. Cell calcification and calcification genes were greatly altered by miR-135a inhibition. KLF4 was validated as the target RNA of miR-135a. Expression of KLF4 and STAT3 were both significantly decreased by over expressed miR-135a, while the inhibition of miR-135a and KLF4 siRNA both decreased the STAT3 protein levels. Moreover, the inhibition of miR-135a dramatically increased the calcium concentration, but co-treatment with KLF4 or STAT3 siRNA both decreased the calcium concentration. The present study identified miR-135a as a potential osteogenic differentiation suppressor in senescent VSMCs and revealed that KLF4/STAT3 pathway, at least partially, was involved in the mechanism.

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Possible involvement of microRNAs in vascular damage in experimental chronic kidney disease

Cited by 72 publications

References 39 publications

Serum microRNAs are altered in various stages of chronic kidney disease: a preliminary study

Serum microRNAs are altered in various stages of chronic kidney disease: a preliminary study

Renal Vein Levels of MicroRNA-26a Are Lower in the Poststenotic Kidney

miR-135a Suppresses Calcification in Senescent VSMCs by Regulating KLF4/STAT3 Pathway

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