Effect of miR-21 on Renal Fibrosis by Regulating MMP-9 and TIMP1 in kk-ay Diabetic Nephropathy Mice

Wang, Jinyang; Gao, Yanbin; Ma, Minglin; Li, Minzhou; Zou, Dawei; Jy, Yang; Zhu, Zhiyao; Zhao, Xuan

doi:10.1007/s12013-013-9539-2

Cited by 129 publications

(117 citation statements)

References 38 publications

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“…It has also been reported that MMPs, such as MMP2 and MMP9, participate in the degradation of the extracellular matrix (ECM), leading to tumor cell invasion (40). Additionally, MMPs are negatively regulated by TIMPs (41). In the present study, we detected the expression levels of proteins related to cell invasion (TIMP1, MMP2 and MMP9) in miR-214 mimic-transfected MCF-7 cells.…”

Section: Discussionmentioning

confidence: 67%

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

Wang

et al. 2015

International Journal of Molecular Medicine

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Abstract. Breast cancer (BC) is the foremost cause of cancerrelated mortality in women worldwide. An increasing number of studies has confirmed that microRNAs (miRNAs or miRs) play an important role in the development and progression of BC. microRNA-214 (miR-214), a member of the miRNA family, has been demonstrated to function as both a tumor suppressor and oncogene in various types of human cancer. However, the biological function of miR-214 in BC remains unclear. The present study was designed to investigate the potential role of miR-214 in the development and progression of BC. Our results revealed that miR-214 expression was significantly increased in the BC tissues compared with the adjacent benign tissues, and that the upregulation of miR-214 was significantly associated with the invasion ability of the BC cells. Furthermore, p53, which has been reported to be downregulated in BC, was predicted to be the target gene of miR-214 using bioinformatics software programs. Moreover, luciferase reporter vectors were constructed and it was confirmed that p53 is a target of miR-214. Following the transfection of miR-214 into BC cells, we found that the overexpression of miR-214 markedly enhanced cell invasion through the downregulation of p53 expression. By contrast, the overexpression of p53 abrogated the effects of miR-214. In conclusion, this study demonstrates that miR-214 functions as an oncogene in BC, at least partly by promoting cell invasion through the downregulation of p53. Therefore, miR-214 may be a potential therapeutic target for the treatment of BC.

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Section: Discussionmentioning

confidence: 67%

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

Wang

et al. 2015

International Journal of Molecular Medicine

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“…В модели ДН у мышей линии KK-Ay увеличение экспрессии miR-21 способствовало развитию почечного фиброза за счет влияния на экспрессию белков, регу-лирующих интенсивность расщепления компонентов ЭЦМ, -матриксной металлопротеиназы-9 и ингиби-тора матриксных металлопротеиназ 1 типа (TIMP-1) [40]. Chau B.N.…”

Section: сахарный диабет Diabetes Mellitusunclassified

New insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targets

Сергеевна²,

Bobkova

et al. 2017

Diabetes mellitus

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Вопросы патогенезаPathogenesis ахарный диабет (СД) -одна из серьезных ме-дико-социальных и экономических проблем современного здравоохранения. Наиболее опасные последствия глобальной эпидемии СД связаны с его сосудистыми осложнениями, в частности с диа-бетической нефропатией (ДН), которая является при-чиной хронической почечной недостаточности (ХПН), высокого сердечно-сосудистого риска, инвалидизации и смертности больных [1]. В этой связи раннее выявле-ние больных СД, предрасположенных к развитию ДН, может служить важным шагом к более эффективным профилактическим и лечебным мероприятиям с целью предотвращения наступления неблагоприятных исходов.Единственным используемым до настоящего вре-мени в рутинной практике методом ранней диагностики ДН является определение микроальбуминурии (МАУ). В современных экспериментальных и клинических ис-следованиях доказана взаимосвязь между альбумину-рией и выраженностью морфологических изменений в почках, однако начальные структурные признаки ДН появляются при еще нормальной экскреции альбумина с мочой, а повышение экскреции альбумина выше нормы

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“…Upregulation of miR-21 by TGF-b could promote ECM expansion and kidney fibrosis by silencing metabolic pathways, regulating MMP-9 and TIMP1 expression, and by activating PTEN/AKT/TORC1 signaling and other pathways. [13][14][15] TGF-b may elevate the miR-21 level by initiating the transcription of genes that encode the essential regulatory elements for miRNA maturation. Smad3 is an upstream molecule of miR-21 that executes TGF-b-induced tissue fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells

Liu

Hong

Wang

et al. 2015

Exp Biol Med (Maywood)

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Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor-b (TGF-b)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF-b-stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-b. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF-b by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), a-smooth muscle actin, and fibroblastspecific protein1 in TGF-b-treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF-b through activation of SphK1. Furthermore, it was observed that TGF-b-stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR 2 also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF-b-stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR 2 siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF-b-induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis.

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Effect of miR-21 on Renal Fibrosis by Regulating MMP-9 and TIMP1 in kk-ay Diabetic Nephropathy Mice

Cited by 129 publications

References 38 publications

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

New insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targets

Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells

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