Atorvastatin ameliorates LPS‐induced inflammatory response by autophagy via AKT/mTOR signaling pathway

Han, Fei; Xiao, Qingqing; Peng, Shi; Che, Xinyu; Jiang, Liang; Shao, Qing; He, Ben

doi:10.1002/jcb.26320

Cited by 47 publications

(32 citation statements)

References 38 publications

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“…suggesting that M1 microglia are increased in AIS patients. We also found that the expression of miR30d-5p was decreased, which is related to autophagy regulation, while autophagy is related to the inflammatory response [42,43]. The results show that miR-30d-5p can significantly suppress ischemia-induced autophagy by targeting both Beclin-1 and Atg5.…”

Section: Discussionmentioning

confidence: 61%

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Jiang

Wang

Jin

et al. 2018

Cell Physiol Biochem

243

191

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Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.

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Section: Discussionmentioning

confidence: 61%

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Jiang

Wang

Jin

et al. 2018

Cell Physiol Biochem

243

191

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“…These results indicated that overexpression of miR‐29a activated the AKT/mTOR signalling pathway by inhibiting PTEN during cardiac hypertrophy. Notably, mTOR is recognized as a negative regulatory factor of autophagy, and the AKT/mTOR pathway is known to regulate autophagy; we thus examined autophagy in pathological cardiac hypertrophy. By transmission electron microscopy, we observed that the number of autophagic vacuoles and autophagosomes in the ventricular septal tissue of TAC‐operated rats was reduced (Figure A).…”

Section: Resultsmentioning

confidence: 99%

miR‐29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy

Shi

Chu

et al. 2019

Acta Physiologica

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Aim: Although miR-29 has emerged as a crucial non-coding RNA in the regulation of pathological cardiac hypertrophy, further exploration of its specific mechanisms is necessary to resolve controversy about its major role in this condition. This study therefore evaluated the role of miR-29a and whether it acts through the PTEN/AKT/ mTOR pathway. Methods: In this study, a rat model of pressure-induced cardiac hypertrophy was established by transverse aortic constriction and verified by echocardiography, histological analysis and quantitative RT-PCR. At the cellular level, we explored the role of miR-29a in angiotensin II-stimulated hypertrophic H9c2 cardiomyoblasts by transfecting the cells with miR-29a inhibitor and mimic. The relationship between miR-29a and the signalling pathway was investigated with dual luciferase reporter assays, immunofluorescence analysis and Western blotting. We also examined whether autophagy is involved in the regulatory mechanism of miR-29a through transmission electron microscopy and detection of autophagy-associated proteins. Results:The results showed that miR-29a was upregulated both in rats 4 weeks after surgery and in 10 −6 M angiotensin II-stimulated cells. In contrast, inhibition of miR-29a partially attenuated angiotensin II-induced hypertrophy. Additionally, bioinformatics analysis revealed that PTEN was one of the target genes of miR-29a, which was also verified by luciferase assay. The results of immunofluorescence and Western blotting indicated that overexpression of miR-29a inhibited the expression of PTEN, activated the AKT/mTOR pathway and suppressed autophagy, which ultimately led to cardiac hypertrophy. Conclusion: In pathological cardiac hypertrophy, miR-29a was overexpressed and promoted cardiac hypertrophy by regulating the PTEN/AKT/mTOR pathway and suppressing autophagy. K E Y W O R D Sautophagy, microRNA-29a, pathological cardiac hypertrophy, PTEN/AKT/mTOR 2 of 12 | SHI et al.How to cite this article: Shi J-Y, Chen C, Xu X, Lu Q. miR-29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy. Acta Physiol.

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“…In addition, LPS‐induced inflammation was closely related to autophagy, which contributed to cell survival and downregulated the production of proinflammatory cytokines (Bussi et al, ; Zeng et al, ). Knockdown of ATG5 with siRNA prevented the role of atorvastatin in decreasing interleukin‐1β and tumor necrosis factor‐α release induced by LPS (Han et al, ). Our results demonstrated that UCA1 was positively correlated with autophagy markers LC3 and inversely correlated with AKT and mTOR after LPS‐induced 4–6 hr in 293T cells.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy

Song

Liang

et al. 2018

Journal Cellular Physiology

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Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been implicated in the growth and metastasis of colorectal cancer (CRC), and autophagy contributes to tumorigenesis and cancer cell survival. However, the regulatory role of UCA1 in CRC cell viability by modulating autophagy remains unclear. In the present study, a significant positive correlation was observed between UCA1 and microtubuleassociated protein 1 light chain 3 (LC3) levels, and the elevated UCA1 was negatively correlated with the PKB/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in 293T cells. Downregulation of UCA1 inhibited autophagy activation and cell proliferation, whereas the apoptosis was increased and the cell cycle was arrested in G2 stage. The next results showed that UCA1 was markedly upregulated in Caco-2 cells. Knockdown of UCA1 significantly decreased the LC3-II and autophagy-related gene 5 (ATG5) protein levels and resulted in an increase in p62 expression. Conversely, the autophagy activator rapamycin (RAPA) reversed the effects. Furthermore, downregulated UCA1 decreased Caco-2 cells population in the G1 phase and increased the cells number in G2 phage. The cell proliferation was inhibited, and apoptosis rate was promoted. More important, RAPA could also abrogate the changes induced by knockdown of UCA1. Collectively, these data demonstrated that downregulated UCA1 induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis, which suggested that UCA1 might serve as a potential new oncogene to regulate CRC cells viability by modulating autophagy. K E Y W O R D S apoptosis, autophagy, cell proliferation, colorectal cancer (CRC) cell, long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1)

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Atorvastatin ameliorates LPS‐induced inflammatory response by autophagy via AKT/mTOR signaling pathway

Cited by 47 publications

References 38 publications

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

miR‐29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy

Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy

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