Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1

Chang, Won Hyuk; Lee, Chang Youn; Park, Jun‐Hee; Park, Moonseo; Maeng, Lee-So; Yoon, Chee Soon; Lee, Min Young; Hwang, Ki‐Chul; Chung, Yong‐An

doi:10.4142/jvs.2013.14.1.69

Cited by 58 publications

(56 citation statements)

References 37 publications

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“…22 The MSC-induced decrease in miR-210 expression in RVD might reflect the changing tissue oxygen environment after MSC delivery, because miR-210 is often related to cell survival under hypoxic condition. 25 Consistent with observations in swine, miR-26a levels were decreased in the stenotic kidney vein in patients with RVD but not the renal vein of patients with EH, linking miR-26a to stenotic kidney damage in renovascular disease. Previous studies showed that miR-26a promotes vascular smooth muscle cell proliferation 7 while inhibiting cellular apoptosis.…”

Section: Discussionsupporting

confidence: 75%

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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Section: Discussionsupporting

confidence: 75%

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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“…miR-210 is a well-known target of HIF and a central player in the hypoxia pathway [23]. A recent report also demonstrated that miR-210 expression positively modulates HIF and correlates with CAIX expression [24]. Intriguingly, our finding of miR-210 up-regulation in CCPRCC could be implicating miR-210 in the activation of the hypoxia pathway in the absence of VHL.…”

Section: Discussionmentioning

confidence: 52%

Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma

et al. 2014

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Summary Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription–polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity.

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“…Interestingly, miR-210/HIF1A positive feedback loop (Fig. 2) may also play an important role in increasing cell survival (25). Moreover, in vitro co-culture experiments show miR-210 transfer from mesenchymal stem cells to cardiomyocytes, indicating that mesenchymal cells may also act as a miRNA delivery system (70).…”

Section: Stem Cells For MI Therapy and Hypoxamirmentioning

confidence: 99%

HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

Greco

Gaetano

Martelli

2014

Antioxidants & Redox Signaling

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Significance: MicroRNAs (miRNAs) are deregulated and play a causal role in numerous cardiovascular diseases, including myocardial infarction, coronary artery disease, hypertension, heart failure, stroke, peripheral artery disease, kidney ischemia-reperfusion. Recent Advances: One crucial component of ischemic cardiovascular diseases is represented by hypoxia. Indeed, hypoxia is a powerful stimulus regulating the expression of a specific subset of miRNAs, named hypoxia-induced miRNAs (hypoxamiR). These miRNAs are fundamental regulators of the cell responses to decreased oxygen tension. Certain hypoxamiRs seem to have a particularly pervasive role, such as miR-210 that is virtually induced in all ischemic diseases tested so far. However, its specific function may change according to the physiopathological context. Critical Issues: The discovery of HypoxamiR dates back 6 years. Thus, despite a rapid growth in knowledge and attention, a deeper insight of the molecular mechanisms underpinning hypoxamiR regulation and function is needed. Future Directions: An extended understanding of the function of hypoxamiR in gene regulatory networks associated with cardiovascular diseases will allow the identification of novel molecular mechanisms of disease and indicate the development of innovative therapeutic approaches.

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Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1

Cited by 58 publications

References 37 publications

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

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

Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma

HypoxamiR Regulation and Function in Ischemic Cardiovascular Diseases

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