Microvesicles containing miR-34a induce apoptosis of proximal tubular epithelial cells and participate in renal interstitial fibrosis

Li, Hongyan; Xu, Yuexia; Zhang, Qin; Xu, Hongfang; Xu, Yan; Ling, Kai

doi:10.3892/etm.2019.7197

Cited by 13 publications

(11 citation statements)

References 26 publications

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“…The majority of these miRNAs have previously been linked to renal diseases, such as RIF. For example, Hou et al (33) found miR-27a to suppress peroxisome proliferator-activated receptor-γ signaling and to thereby promote RIF, whereas miR-34a has been shown to regulate Klotho expression in tubular epithelial cells, thereby controlling RIF (34), while also inducing the apoptotic death of these cells (35). There is also evidence to indicate that miR-214 is upregulated in the context of renal injury, and the knockdown of this miRNA is sufficient to attenuate unilateral ureteral obstruction (UUO)-induced RIF (36).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑101 inhibits renal tubular epithelial‑to‑mesenchymal transition by targeting TGF‑β1 type I receptor

et al. 2021

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MicroRNAs (miRNAs/miRs) are key regulators of renal interstitial fibrosis (RIF). The present study was designed to identify miRNAs associated with the development of RIF, and to explore the ability of these identified miRNAs to modulate the renal tubular epithelial-to-mesenchymal transition (EMT) process. To this end, miRNAs that were differentially expressed between normal and fibrotic kidneys in a rat model of mercury chloride (Hgcl 2 )-induced RIF were detected via an array-based approach. Bioinformatics analyses revealed that miR-101 was the miRNA that was most significantly downregulated in the fibrotic renal tissue samples, and this was confirmed by RT-qPCR, which also demonstrated that this miRNA was downregulated in transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. When miR-101 was overexpressed, this was sufficient to reverse TGF-β1-induced EMT in HK-2 cells, leading to the upregulation of the epithelial marker, E-cadherin, and the downregulation of the mesenchymal marker, α-smooth muscle actin. By contrast, the downregulation of miR-101 using an inhibitor exerted the opposite effect. The overexpression of miR-101 also suppressed the expression of the miR-101 target gene, TGF-β1 type I receptor (TβR-I), and thereby impaired TGF-β1/Smad3 signaling, while the opposite was observed upon miR-101 inhibition. To further confirm the ability of miR-101 to modulate EMT, the HK-2 cells were treated with the TβR-I inhibitor, SB-431542, which significantly suppressed TGF-β1-induced EMT in these cells. Notably, miR-101 inhibition exerted a less pronounced effect upon EMT-related phenotypes in these TβR-I inhibitor-treated HK-2 cells, supporting a model wherein miR-101 inhibits TGF-β1-induced EMT by suppressing TβR-I expression. On the whole, the present study demonstrates that miR-101 is capable of inhibiting TGF-β1-induced tubular EMT by targeting TβR-I, suggesting that it may be an important regulator of RIF.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑101 inhibits renal tubular epithelial‑to‑mesenchymal transition by targeting TGF‑β1 type I receptor

et al. 2021

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“…Overall the results provide evidence in support of beneficial properties of EVs from various sources in prevention or treatment of kidney disorders. However, some EVs secreted by TECs [68][69][70][71][72][73] , fibroblasts 84,85 , platelets 86,87 , podocyte 96 , and MM cells 97 were found to have adverse effects on renal function. Five other studies also suggested that EVs from fibroblasts 25,37,40,77 and T-CD133 + cells 95 may have no beneficial effects on renal injury protection.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effects of extracellular vesicles: a systematic review

Abbaszadeh¹,

Ghorbani²,

Talebi³

et al. 2020

Preprint

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Kidney diseases have recently become one of the major global health problems with high incidence and death risk. Extracellular vesicles (EVs), which are released from most cell types and human body fluids, have recently attracted extensive attention as the important carriers of protective cargos such as microRNAs and proteins that may contribute to promoted renal function.Therefore, we conducted this systematic review to investigate the renoprotective potential of EVs. We performed a comprehensive search of Medline (via PubMed), Embase, Cochrane and Proquest on August, 2019 for English papers. Of 2887 articles met the search criteria, 80 included in this systematic review and classified into several groups based on source of EVs. We then evaluated the EV research through screening their isolation method, size, marker, main effector, and potential mechanisms to induce renal protection. Taken together, EVs from various sources including mesenchymal stem cells, human liver stem cells, endothelial progenitor cells, endothelial colony-forming cells, serum and some other sources might have positive impacts on treatment of human kidney diseases in the future.

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“…Microvesicles, a new cell signaling vector for short- or long-range delivery, contains protein, mRNA and miRNA ( Martins et al, 2013 ; Recep et al, 2017 ). In a study of renal fibrosis, it has been found that ( Zhou et al, 2014 ; Li et al, 2019 ) renal interstitial fibroblasts can secrete microvesicles containing miR-34a to transport to renal tubular epithelial cells and promote their apoptosis; then the microbubbles in fibroblasts can be extracted and injected into cells or mice to imitate the mechanism of miR-34a in renal fibrosis. With the development of science and technology, other better biological agents will likely be found in the future, further improving the treatment of FB.…”

Section: Limitation Of Microrna-34a As Therapeutic Targets Of Fibrosismentioning

confidence: 99%

“…Tubular epithelial cells apoptosis is one of the mechanisms of tubular atrophy and tubulointerstitial fibrosis ( Docherty et al, 2006 ). In the study of rats and mice with renal interstitial fibrosis, miR-34a was released from mesenchymal fibroblasts and transferred to proximal tubular epithelial cells, where it promoted apoptosis of renal tubular epithelial cells by inhibiting the transcription and translation of Bcl-2, further aggravating renal interstitial fibrosis ( Zhou et al, 2014 ; Li et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-34a: A Novel Therapeutic Target in Fibrosis

Min

Qi²,

Liu³

et al. 2022

Front. Physiol.

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Fibrosis can occur in many organs, and severe cases leading to organ failure and death. No specific treatment for fibrosis so far. In recent years, microRNA-34a (miR-34a) has been found to play a role in fibrotic diseases. MiR-34a is involved in the apoptosis, autophagy and cellular senescence, also regulates TGF-β1/Smad signal pathway, and negatively regulates the expression of multiple target genes to affect the deposition of extracellular matrix and regulate the process of fibrosis. Some studies have explored the efficacy of miR-34a-targeted therapies for fibrotic diseases. Therefore, miR-34a has specific potential for the treatment of fibrosis. This article reviews the important roles of miR-34a in fibrosis and provides the possibility for miR-34a as a novel therapeutic target in fibrosis.

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Microvesicles containing miR-34a induce apoptosis of proximal tubular epithelial cells and participate in renal interstitial fibrosis

Cited by 13 publications

References 26 publications

MicroRNA‑101 inhibits renal tubular epithelial‑to‑mesenchymal transition by targeting TGF‑β1 type I receptor

MicroRNA‑101 inhibits renal tubular epithelial‑to‑mesenchymal transition by targeting TGF‑β1 type I receptor

Renoprotective effects of extracellular vesicles: a systematic review

MicroRNA-34a: A Novel Therapeutic Target in Fibrosis

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