Inhibition of the activation of γδT17 cells through PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acid

Yun, Xinming; Fang, Yulai; Lv, Changjun; Qiao, Simiao; Yu, Tao; Dai, Yue; Xia, Yufeng

doi:10.1038/s41419-020-02969-x

Cited by 16 publications

(13 citation statements)

References 69 publications

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“…Conversely, AKT inhibition significantly suppressed osteosarcoma cell proliferation and the malignant phenotype [14,15]. It is well-accepted that AKT is primarily dephosphorylated and inactivated by phosphatase and tensin homolog deleted on chromosome ten (PTEN), a major tumor suppressor gene in humans [16][17][18]. Moreover, inhibiting PTEN activity was capable of promoting osteosarcoma progression through activating AKT pathway [19].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

Sun

Chen

et al. 2022

Analytical Cellular Pathology

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Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues. miR-181a-5p mimic significantly promoted, while miR-181a-5p inhibitor blocked the proliferation, colony formation, migration, invasion, and cell cycle progression of osteosarcoma cells. Mechanistically, miR-181a-5p bound to the 3 ′ -untranslational region of phosphatase and tensin homolog (PTEN) and reduced its protein expression, thereby activating protein kinase B (PKB/AKT) pathway. Either PTEN overexpression or AKT inhibition notably blocked the tumor-promoting effects of miR-181a-5p. Moreover, we observed that miR-181a-5p mimic further inhibited growth of human osteosarcoma cells in the presence of adriamycin or cisplatin. Overall, miR-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway and it is a promising therapeutic target to treat osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

Sun

Chen

et al. 2022

Analytical Cellular Pathology

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“… 17 MA also been reported to have anti-colitis effect by suppressing inflammatory signaling pathway. 31 However, its ability to protect OA chondrocytes has yet to be investigated. As a result, we investigated the anti-inflammatory and protective effects of MA on rat OA chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…22 , 23 According to research, MA can reduce the activation of gammadeltaT17 cells via the Akt/GSK3beta/NFAT pathways, which helps to treat colitis. 16 , 31 In addition, MA may offer promise as a solid and hematological tumor anticancer treatment lead. 22 , 23 Additionally, MA was regarded as an anti-diabetic drug since studies indicated that it may reduce lipid accumulation, attenuate oxidative and inflammatory stress, improve hemostatic imbalance and glycemic control in diabetic mice.…”

Section: Introductionmentioning

confidence: 99%

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study

Fu¹,

He²,

Wang³

et al. 2022

DDDT

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Purpose Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Methods Rat primary chondrocytes were treated with IL-1β to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. Results We found that MA could down-regulate the IL-1β-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1β. Moreover, MA protects chondrocytes from IL-1β-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1β-induced chondrocytes. Conclusion These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

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“… 13 Phosphate and tension homology deleted on chromosome ten (PTEN) is a major negative regulator of AKT phosphorylation and activation, and PTEN upregulation reduces AKT activation and amplifies oxidative damage in Dox‐treated hearts. 14 , 15 Consistently, Johnson et al 16 demonstrated that PTEN inhibitor significantly reduced apoptosis, cardiac remodelling and dysfunction in Dox‐treated mice. In contrast, overexpression of PTEN could exacerbate Dox‐induced cardiomyocyte apoptosis and oxidative stress through blocking AKT pathway.…”

Section: Introductionmentioning

confidence: 85%

“…In addition, AKT activation can suppress the nuclear export and degradation of nuclear factor‐E2‐related factor 2 (NRF2), thereby protecting against Dox‐induced oxidative stress in the heart 13 . Phosphate and tension homology deleted on chromosome ten (PTEN) is a major negative regulator of AKT phosphorylation and activation, and PTEN upregulation reduces AKT activation and amplifies oxidative damage in Dox‐treated hearts 14,15 . Consistently, Johnson et al 16 demonstrated that PTEN inhibitor significantly reduced apoptosis, cardiac remodelling and dysfunction in Dox‐treated mice.…”

Section: Introductionmentioning

confidence: 89%

MicroRNA‐495‐3p diminishes doxorubicin‐induced cardiotoxicity through activating AKT

Meng

2022

J Cellular Molecular Medi

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Doxorubicin (Dox) is identified as a broad-spectrum and efficient chemotherapeutic agent for multiple human solid and hematopoietic cancers; however, adverse cardiovascular events due to the cumulative cardiotoxicity extremely impede its clinical use. [1][2][3] Despite the exact mechanisms of Dox-induced cardiotoxicity remain unclear, reactive oxygen species (ROS) overproduction and oxidative damage are implicated in the pathogenesis of Doxinduced cardiotoxicity. 4,5 Zhang et al. 6 previously has revealed that Dox forms a ternary cleavage complex with topoisomerase-II beta and DNA, which subsequently destroys the structure and function of mitochondria, and leads to excessive ROS generation. In addition, Dox treatment can increase the accumulation of iron inside the mitochondria, and then promote ROS amplification through a Fenton reaction. 7 Moreover, the heart is especially vulnerable to oxidative damage due to the less active antioxidant defence and negligible regenerative capability. 8 Accordingly, our recent study demonstrated that inhibiting oxidative stress significantly prevented Dox-induced cardiotoxicity and dysfunction. 9 Therefore, it is reasonable to treat Dox-induced cardiotoxicity through inhibiting oxidative stress.

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Inhibition of the activation of γδT17 cells through PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acid

Cited by 16 publications

References 69 publications

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study

MicroRNA‐495‐3p diminishes doxorubicin‐induced cardiotoxicity through activating AKT

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