miR‑199b‑5p mediates adriamycin‑induced podocyte apoptosis by inhibiting the expression of RGS10

Qu, Gaoting; He, Tiantian; Dai, Aisuo; Zhao, Yajie; Guan, Dian; Li, Shanwen; Shi, Huimin; Gan, Weihua; Zhang, Aiqing

doi:10.3892/etm.2021.10904

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…Podocyte apoptosis is caused by many factors, including drugs, infection, and immune disorders[ 55 - 57 ]. ADR is one of the drugs that causes podocyte apoptosis due to its pharmacological action and distribution[ 58 ]. However, how to protect podocytes from ADR needs further research to find more effective targeted drugs.…”

Section: Discussionmentioning

confidence: 99%

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis

Hu¹,

Tan²,

Zou³

et al. 2023

World J Stem Cells

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BACKGROUND Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion. However, the protective effect and underlying mechanism of CA-pretreated MSCs (MSCs CA ) on podocytes in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) mice remain unclear. AIM To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved. METHODS ADR was used to induce FSGS in mice, and MSCs, CA, or MSCs CA were administered to mice. Their protective effect and possible mechanism of action on podocytes were observed by Western blot, immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction. In vitro , ADR was used to stimulate mouse podocytes (MPC5) to induce injury, and the supernatants from MSC-, CA-, or MSCs CA -treated cells were collected to observe their protective effects on podocytes. Subsequently, the apoptosis of podocytes was detected in vivo and in vitro by Western blot, TUNEL assay, and immunofluorescence. Overexpression of Smad3, which is involved in apoptosis, was then induced to evaluate whether the MSCs CA -mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells. RESULTS CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells. Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells, which was reversed by MSC CA treatment more significantly than by MSCs or CA alone. When Smad3 was overexpressed in MPC5 cells, MSCs CA could not fulfill their potential to inhibit podocyte apoptosis. CONCLUSION MSCs CA enhance the protection of MSCs against ADR-induced podocyte apoptosis. The underlying mechanism may be related to MSCs CA -targeted inhibition of p-Smad3 in podocytes.

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Section: Discussionmentioning

confidence: 99%

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis

Hu¹,

Tan²,

Zou³

et al. 2023

World J Stem Cells

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“…Total RNAs (including mRNA and microRNA) was purified from kidney and mTECs using TRIzol® reagent (Life Technologies; Agilent, Inc., USA). RT‐qPCR was performed and analysed as described previously 19 . The primers sequences are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…RT‐qPCR was performed and analysed as described previously. 19 The primers sequences are shown in Table 1 . The thermocycling conditions were presented in Tables 2 and 3 .…”

Section: Methodsmentioning

confidence: 99%

MicroRNA‐26a alleviates tubulointerstitial fibrosis in diabetic kidney disease by targeting PAR4

Qu,

Li,

Jin

et al. 2024

J Cellular Molecular Medi

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Our previous study found that miR‐26a alleviates aldosterone‐induced tubulointerstitial fibrosis (TIF). However, the effect of miR‐26a on TIF in diabetic kidney disease (DKD) remains unclear. This study clarifies the role and possible mechanism of exogenous miR‐26a in controlling the progression of TIF in DKD models. Firstly, we showed that miR‐26a was markedly decreased in type 2 diabetic db/db mice and mouse tubular epithelial cells (mTECs) treated with high glucose (HG, 30 mM) using RT‐qPCR. We then used adeno‐associated virus carrying miR‐26a and adenovirus miR‐26a to enhance the expression of miR‐26a in vivo and in vitro. Overexpressing miR‐26a alleviated the TIF in db/db mice and the extracellular matrix (ECM) deposition in HG‐stimulated mTECs. These protective effects were caused by reducing expression of protease‐activated receptor 4 (PAR4), which involved in multiple pro‐fibrotic pathways. The rescue of PAR4 expression reversed the anti‐fibrosis activity of miR‐26a. We conclude that miR‐26a alleviates TIF in DKD models by directly targeting PAR4, which may provide a novel molecular strategy for DKD therapy.

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“…Lin et al (2018) recently described Enterococcus faecalis as a causative agent of persistent apical periodontitis with the ability to augment autophagy by suppressing the PI3K/Akt/mTOR signalling pathway in macrophages; this may lead to persistent inflammation in the periapical region, highlighting the relationship between autophagy and apical periodontitis. It has been reported that overexpression of RGS10 in kidney diseases can inhibit the mTOR signalling pathway, which is a known negative regulator of TFEB (Napolitano et al, 2018; Qu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

RGS10 negatively regulates apical periodontitis via TFEB‐mediated autophagy in BABL/c mice model and in vitro

Yuan

Chan

et al. 2023

Int Endodontic J

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Aim Apical periodontitis is a prevalent oral inflammatory disease that has recently been linked to transcription factor EB (TFEB)‐mediated autophagy. Regulator of G‐protein signalling 10 (RGS10) is reported to be an effective regulator of the immune system and inflammation. This study aimed to investigate the involvement of RGS10 during the development of apical periodontitis through the TFEB‐mediated autophagy signalling pathway. Methodology Sixty BALB/c mice were randomly divided into four groups of 15 mice for the in vivo experiment. Rgs10 was locally overexpressed through eight injections of an adeno‐associated virus vector. The model of apical periodontitis was established 21 days following pulp exposure, and the mice were euthanized to obtain mandibles for analysis. Micro‐computed tomography was employed to assess alveolar bone destruction, and the levels of Rgs10, TFEB‐mediated autophagy signalling factors and inflammatory factors were measured using quantitative reverse transcription polymerase chain reactions, western blotting, enzyme‐linked immunosorbent assays, immunofluorescence and immunohistochemistry. All experimental results were displayed as images or graphs. For the in vitro experiments, we employed small interfering RNA (siRNA) to silence Rgs10 expression in RAW 264.7 cells. The data were analysed via one‐way anova or Mann–Whitney U test/Kruskal–Wallis test of variance, where p < .05 or U > 1.96 was considered statistically significant. Results Local overexpression of Rgs10 reduced alveolar bone destruction within the apical periodontitis lesion and significantly decreased macrophage infiltration (p < .05). Meanwhile, the expression of TFEB‐mediated autophagy signalling factors was upregulated, along with a decrease in inflammatory factor expression (p < .05). Lipopolysaccharide‐stimulated RAW 264.7 cells exhibited decreased Rgs10 expression and TFEB‐mediated autophagy signalling. siRNA‐mediated silencing of Rgs10 further suppressed autophagy and concomitantly upregulated inflammatory factors (p < .05). Conclusions Collectively, the findings revealed that RGS10 suppresses the inflammatory response and bone destruction through TFEB‐mediated autophagy in apical periodontitis.

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miR‑199b‑5p mediates adriamycin‑induced podocyte apoptosis by inhibiting the expression of RGS10

Cited by 5 publications

References 35 publications

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis

MicroRNA‐26a alleviates tubulointerstitial fibrosis in diabetic kidney disease by targeting PAR4

RGS10 negatively regulates apical periodontitis via TFEB‐mediated autophagy in BABL/c mice model and in vitro

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