miR-129-5p alleviates LPS-induced acute kidney injury via targeting HMGB1/TLRs/NF-kappaB pathway

Huang, Xin; Hou, Xiangping; Chuan, Libo; Wei, Shutao; Wang, Jingrong; Yang, Xiaohua; Jin, Ran

doi:10.1016/j.intimp.2020.107016

Cited by 39 publications

(26 citation statements)

References 41 publications

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“…miR-129-5p could significantly inhibit adipocyte differentiation through autophagy and may be a target for the treatment of obesity [25]. The study also revealed that miR-129-5p alleviated acute kidney injury via targeting the HMGB1/TLRs/NF-κB pathway [26].…”

Section: Stem Cells Internationalmentioning

confidence: 81%

miR-129-5p Promotes Osteogenic Differentiation of BMSCs and Bone Regeneration via Repressing Dkk3

Zhao

Wang

et al. 2021

Stem Cells International

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Objective. Accumulating evidence indicates that microRNAs (miRNAs) play crucial roles in osteogenic differentiation. However, the associated mechanisms remain elusive. This paper is aimed at exploring the role of miR-129-5p in regulating bone marrow mesenchymal stem cell (BMSC) differentiation and bone regeneration in vivo and in vitro. Methods. BMSCs were transduced by miR-129-5p mimic, miR-129-5p inhibitor, and negative control lentivirus. The ability of BMSC differentiation to osteoblast was tested by alkaline phosphatase (ALP) and alizarin red staining (ARS). The expression of osteogenic genes (Runx2, Bmp2, and OCN) was examined via quantitative RT-PCR and western blot. A mouse model of calvaria defect was investigated by Micro-CT, immunohistochemistry, and histological examination. The luciferase reporter gene assay was performed to confirm the binding between Dkk3 and miR-129-5p. For the transfection experiments, lipofectamine 3000 was used to transfect pcDNA-Dkk3 into BMSCs to overexpress Dkk3. Coimmunoprecipitation and immunofluorescent localization assay were included for exploring the role of Dkk3 and β-catenin. Results. miR-129-5p was induced in BMSCs and MSC cell line C3H10T1/2 cells under osteogenic medium. Overexpression of miR-129-5p significantly promoted osteogenic differentiation of BMSCs in vitro. Moreover, BMSCs transduced with miR-129-5p mimic exhibited better bone regeneration compared with BMSCs transduced with control counterpart in vivo. Luciferase and western blot data showed that Dickkopf3 (Dkk3) is a target gene of miR-129-5p and the expression of Dkk3 was inhibited in BMSCs transduced with miR-129-5p mimic but enhanced in BMSCs transduced with miR-129-5p inhibitor. In addition, Dkk3 interacted with β-catenin directly. Conclusions. miR-129-5p promotes osteogenic differentiation of BMSCs and bone regeneration, and miR-129-5p/Dkk3 axis may be new potential targets for the treatment of bone defect and bone loss.

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Section: Stem Cells Internationalmentioning

confidence: 81%

miR-129-5p Promotes Osteogenic Differentiation of BMSCs and Bone Regeneration via Repressing Dkk3

Zhao

Wang

et al. 2021

Stem Cells International

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“…MiR-106a promotes the sepsis-associated AKI via downregulating THBS2 in vivo (Shen et al, 2019). Furthermore, miR-129-5p attenuates LPS-stimulated AKI by regulating HMGB1/TLRs/NF-κB signaling (Huang et al, 2020). TNF-α/HMGB1 signaling is involved in proptosis in AKI .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA TLK1 Promotes Sepsis-Associated Acute Kidney Injury by Regulating Inflammation and Oxidative Stress Through miR-106a-5p/HMGB1 Axis

Yang

2021

Front. Mol. Biosci.

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Sepsis is an inflammatory disorder and leads to severe acute kidney injury (AKI). Circular RNAs (circRNAs) have been identified as a critical type of regulatory noncoding RNAs (ncRNAs) that present the important functions in various diseases. In this study, we identified a novel circRNA circTLK1 in the regulation of sepsis-induced AKI. We observed that circTLK1 expression was elevated in the cecal ligation and puncture (CLP) rat model compared with that in the control rats. The urine levels of neutrophil gelatinase–associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) and the serum levels of creatinine (sCr) and blood urea nitrogen (BUN) were increased by the CLP treatment in the rats but were blocked by the circTLK1 shRNA. The circTLK1 shRNA reduced the CLP-induced kidney injury in the rats. The circTLK1 knockdown repressed oxidation stress, inflammation, and apoptosis in the sepsis-related AKI rat model. Moreover, lipopolysaccharide (LPS) treatment increased the production of TNF-α, IL-1β, and IL-6 in the HK-2 cells, while the circTLK1 shRNA could attenuate the enhancement in the cells. Bax and cleaved caspase-3 expression was upregulated, but Bcl-2 expression was downregulated by the LPS in the HK-2 cells, in which circTLK1 depletion reversed this effect in the cells. The depletion of circTLK1 attenuated the LPS-induced apoptosis in the HK-2 cells. CircTLK1 enhanced HMGB1 expression by sponging miR-106a-5p in the HK-2 cells, and miR-106a-5p and HMGB1 were involved in circTLK1-meidated injury of LPS-treated cells. Therefore, we concluded that circTLK1 contributed to sepsis-associated AKI by regulating inflammation and oxidative stress through the miR-106a-5p/HMGB1 axis. CircTLK1 and miR-106a-5p may be employed as the potential targets for the treatment of AKI.

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“…This finding is consistent with previous reports and indicates the reliability of the microarray results in the present study. However, miR-129 was selected for further investigation as it exhibited the most statistically significant difference between the two groups and as previous studies have discussed the role of miR-129 in regulating injury and inflammatory response in different organ injury models ( 19 , 38 , 39 ).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‑129 plays a protective role in sepsis‑induced acute lung injury through the suppression of pulmonary inflammation via the modulation of the TAK1/NF‑κB pathway

et al. 2021

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Excessive inflammatory response and apoptosis play key roles in the pathogenic mechanisms of sepsis-induced acute lung injury (ALI); however, the molecular pathways linked to ALI pathogenesis remain unclear. Recently, microRNAs (miRNAs/miRs) have emerged as important regulators of inflammation and apoptosis in sepsis-induced ALI; however, the exact regulatory mechanisms of miRNAs remain poorly understood. In the present study, the gene microarray dataset GSE133733 obtained from the Gene Expression Omnibus database was analyzed and a total of 38 differentially regulated miRNAs were identified, including 17 upregulated miRNAs and 21 downregulated miRNAs, in mice with lipopolysaccharide (LPS)-induced ALI, in comparison to the normal control mice. miR-129 was found to be the most significant miRNA, among the identified miRNAs. The upregulation of miR-129 markedly alleviated LPS-induced lung injury, as indicated by the decrease in lung permeability in and the wet-to-dry lung weight ratio, as well as the improved survival rate of mice with ALI administered miR-129 mimic. Moreover, the upregulation of miR-129 reduced pulmonary inflammation and apoptosis in mice with ALI. Of note, transforming growth factor activated kinase-1 (TAK1), a well-known regulator of the nuclear factor-κB (NF-κB) pathway, was directly targeted by miR-129 in RAW 264.7 cells. More importantly, miR-129 upregulation impeded the LPS-induced activation of the TAK1/NF-κB signaling pathway, as illustrated by the suppression of the nuclear phosphorylated-p65, p-IκB-α and p-IKKβ expression levels. Collectively, the findings of the present study indicate that miR-129 protects mice against sepsis-induced ALI by suppressing pulmonary inflammation and apoptosis through the regulation of the TAK1/NF-κB signaling pathway. This introduces the basis for future research concerning the application of miR-129 and its targets for the treatment of ALI.

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miR-129-5p alleviates LPS-induced acute kidney injury via targeting HMGB1/TLRs/NF-kappaB pathway

Cited by 39 publications

References 41 publications

miR-129-5p Promotes Osteogenic Differentiation of BMSCs and Bone Regeneration via Repressing Dkk3

miR-129-5p Promotes Osteogenic Differentiation of BMSCs and Bone Regeneration via Repressing Dkk3

Circular RNA TLK1 Promotes Sepsis-Associated Acute Kidney Injury by Regulating Inflammation and Oxidative Stress Through miR-106a-5p/HMGB1 Axis

MicroRNA‑129 plays a protective role in sepsis‑induced acute lung injury through the suppression of pulmonary inflammation via the modulation of the TAK1/NF‑κB pathway

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