MiR-30a Inhibits the Epithelial—Mesenchymal Transition of Podocytes through Downregulation of NFATc3

Peng, Rui; Zhou, Li; Zhou, Yuru; Zhao, Yunfeng; Li, Qianyin; Ni, Dongsheng; Hu, Yanxia; Long, Yaoshui; Liu, Jianing; Lyu, Zhong-Shi; Mao, Zhizhong; Yuan, Yue; Huang, Liyuan; Zhao, Hui; Ge, Li; Zhou, Qin

doi:10.3390/ijms161024032

Cited by 24 publications

(21 citation statements)

References 40 publications

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“…HG addition is able to induce the increase of micro-RNA-346 which is a concentration-dependent effect, and miR-346 mimic significantly inhibits EMT of podocytes by indirectly decreasing the expression of GSK-3β [38]. In podocytes, miR-30a significantly enhanced the expression of E-cadherin, an EMT marker, blocking the podocyte EMT by targeting NFATc3 [39]. These studies indicate that miRNAs play a pivotal role in regulating podocyte EMT.…”

Section: Discussionmentioning

confidence: 75%

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

Jin

Wang

Zhao

et al. 2020

BioMed Research International

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Background. Podocyte migration is actively involved in the process of podocyte loss and proteinuria production, which is closely associated with the development of diabetic nephropathy (DN). Exosomes from adipose-derived stem cells (ADSCs-Exos) effectively inhibit podocyte apoptosis in the treatment of DN. However, how ADSCs-Exos affect the migration of podocytes is obscure. This study is aimed at exploring the regulatory role of ADSCs-Exos on cell migration and the underlying mechanism. Methods. ADSCs-Exo was authenticated by transmission electron microscopy (TEM), western blotting, and flow cytometry. Cell viability and migration ability of podocytes were measured by CCK8 and Transwell assays, respectively. Relative expressions of miRNAs and mRNAs were determined by qRT-PCR. The transmitting between PKH26-labeled exosome and podocytes was evaluated by IF assay. Dual luciferase reporter assay was employed to detect the relationship between miR-215-5p and ZEB2. Results. The exposure to serum from DN patient (hDN-serum) significantly inhibited cell viability of podocytes, but ADSCs-Exo addition notably blunts cytotoxicity induced by the transient stimulus of hDN-serum. Besides, ADSCs-Exo administration powerfully impeded high glucose-(HG-) induced migration and injury of podocyte. With the podocyte dysfunction, several miRNAs presented a significant decline under the treatment of HG including miR-251-5p, miR-879-5p, miR-3066-5p, and miR-7a-5p, all of which were rescued by the addition of ADSCs-Exo. However, only miR-251-5p was a key determinant in the process of ADSCs-Exo-mediated protective role on podocyte damage. The miR-251-5p inhibitor counteracted the improvement from the ADSCs-Exo preparation on HG-induced proliferation inhibition and migration promotion. Additionally, miR-215-5p mimics alone remarkably reversed HG-induced EMT process of podocyte. Mechanistically, we confirmed that ADSCs-Exos mediated the shuttling of miR-215-5p to podocyte, thereby protecting against HG-induced metastasis, possibly through inhibiting the transcription of ZEB2. Conclusion. ADSCs-Exo has the protective effect on HG-evoked EMT progression of podocytes thru a mechanism involving ZEB2. Potentially, the ADSCs-Exo preparation is a useful therapeutic strategy for improving podocyte dysfunction and DN symptoms clinically.

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Section: Discussionmentioning

confidence: 75%

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

Jin

Wang

Zhao

et al. 2020

BioMed Research International

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“…Angiotensin II has been shown to induce calcineurin signaling and podocyte injury by reducing miR-30, indicating that miR-30 expression might be protective for podocyte [51]. miR-30e has been shown to target Bnip3L and protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction [52]. miR-30a has also been shown to inhibit EMT of podocyte through downregulation of NFATc3 [53].…”

Section: Versatile Msc-evs-derived Mirnas Modulate Renal Injury and Hmentioning

confidence: 99%

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

Tsuji

Kitamura

Wada

2020

IJMS

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Mesenchymal stem cells (MSCs) have immunomodulatory and regenerative effects in many organs, including the kidney. Emerging evidence has shown that the trophic effects from MSCs are mainly mediated by the paracrine mechanism rather than the direct differentiation of MSCs into injured tissues. These secretomes from MSCs include cytokines, growth factors, chemokines and extracellular vesicles (EVs) containing microRNAs, mRNAs, and proteins. Many research studies have revealed that secretomes from MSCs have potential to ameliorate renal injury in renal disease models, including acute kidney injury and chronic kidney disease through a variety of mechanisms. These trophic mechanisms include immunomodulatory and regenerative effects. In addition, accumulating evidence has uncovered the specific factors and therapeutic mechanisms in MSC-derived EVs. In this article, we summarize the recent advances of immunomodulatory and regenerative effects of EVs from MSCs, especially focusing on the microRNAs.

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“…Peng et al . 16 reported that miR‐30a can inhibit the epithelial–mesenchymal transition. Zhu et al .…”

Section: Introductionmentioning

confidence: 99%

“…Du et al [13] identified 18 downregulated and 19 up-regulated miRNAs in fibrotic livers, of which miR-30a was down-regulated in a NASH model in C57BL/6 mice, and studies have reported that miR-30a is a key regulator of myocardial fibrosis [14] and peritoneal fibrosis [15]. Peng et al [16] reported that miR-30a can inhibit the epithelial-mesenchymal transition. Zhu et al [17] reported that Beclin1, a key autophagy-related gene, was a possible target for miR-30a, which negatively regulated Beclin1 to inhibit autophagic activity.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐30a ameliorates hepatic fibrosis by inhibiting Beclin1‐mediated autophagy

Chen

et al. 2017

J Cellular Molecular Medi

100

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We explored the role of microRNA‐30a (miR‐30a) and the mechanism involved in hepatic fibrosis. MiR‐30a overexpression was achieved by miR‐30a mimics transfection in hepatic stellate cells (HSCs) (HSC‐T6, LX‐2), and miR‐30a agomir (ago‐miR‐30a) treatment in mice. MiR‐30a levels were measured using TaqMan miRNA assay system, and the localization of miR‐30a was detected by fluorescence in situ hybridization (FISH). The interaction of miR‐30a and Beclin1 was confirmed by dual‐luciferase reporter assay. Autophagic flux was analysed using tandem mRFP‐GFP‐LC3 fluorescence microscopy, electron microscopy and Western blot of LC3‐II/I ratio. MiR‐30a was notably down‐regulated in activated HSCs and LX‐2‐exosomes induced by TGF‐β1; overexpression of miR‐30a down‐regulated extracellular matrix (ECM), such as α‐SMA, TIMP‐1, and Collagen I expression, and suppressed cell viability in HSCs. MiR‐30a was significantly down‐regulated in hepatic fibrosis mice and overexpression of miR‐30a prevented BDL‐induced fibrogenesis, concomitant with the down‐regulation of ECM. MiR‐30a inhibited HSCs autophagy and increased lipid accumulation in HSCs and in mice fibrotic hepatic tissues. MiR‐30a inhibited its downstream effector of Beclin1 by direct targeting its 3′‐UTR region. Moreover, Knock‐down of Beclin1 by small interfering RNA (siRNA) inhibited HSC autophagy and activation in LX‐2 cells. In conclusion, miR‐30a is down‐regulated in hepatic fibrosis models and its overexpression prevents liver fibrogenesis by directly suppressing Beclin1‐mediated autophagy; therefore, miR‐30a may be a new potential therapeutic target for controlling hepatic fibrosis.

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MiR-30a Inhibits the Epithelial—Mesenchymal Transition of Podocytes through Downregulation of NFATc3

Cited by 24 publications

References 40 publications

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

MicroRNA‐30a ameliorates hepatic fibrosis by inhibiting Beclin1‐mediated autophagy

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