Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

Zhang, Yue; Huang, Hongdong; Liu, Wenhu; Li, Sha; Wang, Xue Yan; Diao, Zong Li; Zhang, Ai Hua; Wei, Guo; Han, Xue; Dong, Xiaoqun; Katilov, Oleksandr

doi:10.1038/s41419-021-03578-y

Cited by 53 publications

(29 citation statements)

References 34 publications

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“…As for HK2, PKM2, LDHA, and GLUT1 proteins detection, GAPDH, another glycolytic enzyme (Liao et al, 2019), was used as the loading control. The present study showed no effect of miR-21-5p on GAPDH expression, as indicated by no statistical difference of gray value in different group, which was in consistence with previous studies that miR-21-5p inhibition or overexpression did not affect GAPDH expression (Huang et al, 2021;Zhang et al, 2021) As an important characteristic of metabolic reprogramming in tumor cells, the Warburg effect contrib- utes to growth, survival, and proliferation of cancer stem cells (CSCs) as well as enables the maintenance of the CSCs state (Vaupel et al, 2019). Tumorigenic cells with stem cell-like characteristics are regarded as CSCs, which have strong multi-directional differentiation potential and self-renewal ability (Ayob & Ramasamy, 2018;Hajizadeh et al, 2019).…”

Section: Discussionsupporting

confidence: 92%

“…Epidemiological investigation indicated that three out of every million young adults and children suffer from OS, and the incidence reaches a peak at 11-15 years of age with six in every million children (Lu et al, 2020). Although much effort has been dedicated to OS therapy, the five-year survival and prognosis of OS patients remain unimproved, particularly for patients with recurrence, multidrug resistance, or lung metastasis, due to insufficient diagnosis at the early stage and ineffective therapeutic approaches (Zhang et al, 2018). Therefore, it is necessary to identify novel clinical prognostic biomarkers and investigate the potential molecular mechanisms of OS to develop more effective therapeutic strategies (Tu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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MiR-21-5p inhibition attenuates Warburg effect and stemness maintenance in osteosarcoma cells via inactivation of Wnt/β-catenin signaling

Zhong

et al. 2021

Acta Biochim Pol

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MicroRNA (miR)-21 has been found to be overexpressed in osteosarcoma (OS). The aim of the present study was to investigate the effect of miR-21-5p on the Warburg effect and stemness maintenance in OS cells and its potential molecular mechanism. Herein, miR-21-5p was overexpressed or inhibited in MG-63 cells via transfection with mimics or inhibitors. The effect of miR-21-5p on cell viability, apoptosis, Warburg effect and stemness maintenance were explored in OS cells. The results demonstrated that miR-21-5p inhibition suppressed MG-63 cell viability and enhanced their apoptosis. Additionally, miR-21-5p inhibition attenuated the stemness maintenance of MG-63 cells, as demonstrated by the reduced proportion of CD133-positive MG-63 cells, the decrease in tumorsphere formation capacity, and the downregulation of Sox2, Oct4, and Nanog proteins. Moreover, miR-21-5p inhibition suppressed the Warburg effect in MG-63 cells, as indicated by the decrease in glucose uptake, lactic acid production, and ATP level and the downregulation of proteins involved in the Warburg effect (GLUT1, LDHA, HK2, and PKM2). Furthermore, the results suggested that the effect of miR-21-5p suppression on stemness and the Warburg effect may be associated with the decreased activity of the Wnt/β-catenin pathway in OS cells. Our findings suggest a novel potential biomarker for OS therapy.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

MiR-21-5p inhibition attenuates Warburg effect and stemness maintenance in osteosarcoma cells via inactivation of Wnt/β-catenin signaling

Zhong

et al. 2021

Acta Biochim Pol

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“…In recent studies, a number of exosomal proteins, miRNAs and lncRNAs have been reported to promote the progression of AKI. For example, Cao et al ( 14 ) found that exosomal miR-125b-5p deriving from mesenchymal stem cells (MSCs) could promote tubular repair by suppression of p53 in ischemic AKI; Zhang et al ( 23 ) indicated that endothelial progenitor cells-derived exosomal miR-21-5p could alleviate sepsis-induced AKI by inhibiting runt-related transcription factor 1 expression. However, the function of exosomes in AKI needs to be further explored.…”

Section: Introductionmentioning

confidence: 99%

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Zhang

Zheng

et al. 2021

Mol Med Rep

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Acute kidney injury (AKI) poses a severe threat to human health. MicroRNAs (miRNAs/miRs) are known to be involved in the progression of AKI; however, the function of miR-1184 in AKI remains unclear. Thus, the aim of the present study was to examine the role of this miRNA in kidney injury. In order to mimic AKI in vitro , HK-2 cells were treated with cisplatin. Bioinformatics analysis was performed to explore the differentially expressed miRNAs in AKI. A Cell Counting Kit-8 assay and flow cytometry were performed to examine cell viability and apoptosis, respectively. mRNA expression levels were detected via reverse transcription-quantitative PCR, and protein levels were investigated by western blot analysis. ELISA was performed to examine the levels of IL-1β and TNF-α in the cell supernatants. The results revealed that miR-1184 expression was downregulated in AKI. Exosomes derived from miR-1184 agomir-treated mesenchymal stem cells (MSCs) significantly reversed cisplatin-induced cell growth inhibition by inhibiting apoptosis. Moreover, forkhead box O4 (FOXO4) was found to be the direct target of miR-1184, and exosomes expressing miR-1184 notably inhibited cisplatin-induced inflammatory responses in HK-2 cells via the mediation of IL-1β and TNF-α. Furthermore, exosomes derived from miR-1184 agomir-treated MSCs significantly induced G 1 phase arrest in HK-2 cells via the regulation of FOXO4, p27 Kip1 and CDK2. In conclusion, the present study demonstrated that exosomal-miR-1184 derived from MSCs alleviates cisplatin-associated AKI. Thus, the findings presented herein may shed new light onto the exploration of novel strategies for the treatment of AKI.

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“…miRNAs are a type of short endogenous non-coding molecules with about 18-25 nucleotides 154 . The dysregulation of miRNAs is closely related to the pathophysiological process of AKI 155 - 165 . For example, the level of miRNA-21 in AKI patients is more than five times higher than that in healthy persons.…”

Section: Mirna-21mentioning

confidence: 99%

Emerging early diagnostic methods for acute kidney injury

Xiao¹,

Huang²,

Yang³

et al. 2022

Theranostics

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Many factors such as trauma and COVID-19 cause acute kidney injury (AKI). Late AKI have a very high incidence and mortality rate. Early diagnosis of AKI provides a critical therapeutic time window for AKI treatment to prevent progression to chronic renal failure. However, the current clinical detection based on creatinine and urine output isn't effective in diagnosing early AKI. In recent years, the early diagnosis of AKI has made great progress with the advancement of information technology, nanotechnology, and biomedicine. These emerging methods are mainly divided into two aspects: First, predicting AKI through models construct by machine learning; Second, early diagnosis of AKI through detection of newly-discovered early biomarkers. Currently, these methods have shown great potential and become an attractive tool for the early diagnosis of AKI. Therefore, it is very important to discuss and summarize these methods for the early diagnosis of AKI. In this review, we first systematically summarize the application of machine learning in AKI prediction algorithms and specific scenarios. In addition, we introduce the key role of early biomarkers in the progress of AKI, and then comprehensively summarize the application of emerging detection technologies for early AKI. Finally, we discuss current challenges and prospects of machine learning and biomarker detection. The review is expected to provide new insights for early diagnosis of AKI, and provided important inspiration for the design of early diagnosis of other major diseases.

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Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

Cited by 53 publications

References 34 publications

MiR-21-5p inhibition attenuates Warburg effect and stemness maintenance in osteosarcoma cells via inactivation of Wnt/β-catenin signaling

MiR-21-5p inhibition attenuates Warburg effect and stemness maintenance in osteosarcoma cells via inactivation of Wnt/β-catenin signaling

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Emerging early diagnostic methods for acute kidney injury

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