TERT alleviates irradiation-induced late rectal injury by reducing hypoxia-induced ROS levels through the activation of NF-κB and autophagy

Liu, Qi; Sun, Yong; Lv, Yuefeng; Le, Ziyu; Xin, Yuhu; Zhang, Ping; Liu, Yong

doi:10.3892/ijmm.2016.2673

Cited by 17 publications

(13 citation statements)

References 37 publications

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“…Next, we explored whether CAG had a protective role on TERT in primary human EpSCs. TERT, a reverse transcriptase of telomerase has been shown to be involved in certain types of injury through the activation of specific signals, such as NF-kappa B and autophagy [24], and it may have noncanonical functions in regulating the expression of particular genes [18]. As expected, in our real-time qPCR and western blot analysis, we found a significantly increased expression of TERT in EpSCs, which was related to improved proliferation and migration abilities.…”

Section: Discussionsupporting

confidence: 83%

The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

Cao

Yang

et al. 2019

BioMed Research International

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Background. Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden. Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes. The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds. Methods. Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor). A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and β-catenin knockdown cell line. Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration. The activation of TERT, β-catenin, and c-Myc was determined using real-time qPCR and western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/β-catenin signals. Results. CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, β-catenin, c-Myc. These effects of CAG were most pronounced at a dose of 0.3 μM. Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and β-catenin-silenced cells. In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/β-catenin signaling. Conclusion. Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/β-catenin signaling.

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Section: Discussionsupporting

confidence: 83%

The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

Cao

Yang

et al. 2019

BioMed Research International

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“…Hypoxia is a known inducer of autophagy (34). The present study demonstrated that the induction of autophagy and ROS production under hypoxic conditions, and autophagy inhibition by 3MA, led to a higher level of ROS production and cell apoptosis in R + and R − cells, which is in agreement with a previous study (35). …”

Section: Discussionsupporting

confidence: 94%

Insulin-like growth factor 1 receptor-mediated cell survival in hypoxia depends on the promotion of autophagy via suppression of the PI3K/Akt/mTOR signaling pathway

Liu

Guan

Sun

et al. 2017

Molecular Medicine Reports

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Hypoxia is widely accepted as a fundamental biological phenomenon, which is strongly associated with tissue damage and cell viability under stress conditions. Insulin-like growth factor-1 (IGF-1) is known to protect tissues from multiple types of damage, and protect cells from apoptosis. Hypoxia is a regulatory factor of the IGF system, however the role of the IGF-1 receptor (IGF-1R) in hypoxia-induced apoptosis remains unclear. The present study investigated the potential mechanisms associated with IGF-1R-associated apoptosis under hypoxic conditions. Mouse embryonic fibroblasts exhibiting disruption or overexpression of IGF-1R (R- cells and R+ cells) were used to examine the level of apoptosis, autophagy, and production of reactive oxygen species (ROS). The autophagy inhibitor 3-methyladenine was used to assess the effect of autophagy on ROS production and apoptosis under hypoxic conditions. A potential downstream signaling pathway involving phosphatidylinositol 3-kinase (PI3K)/threonine protein kinase B (Akt)/mammalian target of rapamycin (mTOR) was identifiedby western blot analysis. The results demonstrated that hypoxia induced apoptosis, increased ROS production, and promoted autophagy in a time-dependent manner relative to that observed under normoxia. R+ cells exhibited a lower percentage of apoptotic cells, lower ROS production, and higher levels of autophagy when compared to that of R- cells. In addition, inhibition of autophagy led to increased ROS production and a higher percentage of apoptotic cells in the two cell types. Furthermore, IGF-1R is related with PI3K/Akt/mTOR signaling pathway and enhanced autophagy-associated protein expression, which was verified following treatment with the PI3K inhibitor LY294002. These results indicated that IGF-1R may increase cell viability under hypoxic conditions by promoting autophagy and scavenging ROS production, which is closed with PI3K/Akt/mTOR signaling pathway.

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“…HO-1/BM-MSCs-treated group had the highest level of autophagy-related proteins LC3 II and Beclin-1, which suggested that significant amounts of autophagy occurred in the HO-1/BM-MSCs-treated group, and was consistent with ultrastructure results of the transplanted livers. Previous studies indicated that autophagy, as a cytoprotective mechanism, is involved in biological process such as growth, development and immune regulation ( 14 , 31 ). In addition, autophagy could relieve ischemia-reperfusion injury and induce immune tolerance in the organ transplantation ( 16 , 17 , 32 – 37 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of heme oxygenase-1-transduced bone marrow-derived mesenchymal stem cells on reduced-size liver transplantation: Role of autophagy regulated by the ERK/mTOR signaling pathway

Wang

Shen

Liu

et al. 2017

International Journal of Molecular Medicine

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Autophagy is a critical lysosomal pathway that degrades cytoplasmic components to maintain cell homeostasis and provide substrates for energy metabolism. A study revealed that heme oxygenase-1 (HO-1)-transduced bone marrow-derived mesenchymal stem cells (BM-MSCs) could protect 50% reduced-size liver transplantation (RSLT) in a rat model. However, the mechanisms remain mostly unknown. The aim of the present study was to explore the effects and related mechanism of autophagy on the protection conferred by HO-1-transduced BM-MSCs (HO-1/BM-MSCs) on 50% RSLT in a rat model. The authors established an acute rejection model following 50% RSLT in rats, with recipients divided into three groups receiving treatment with BM-MSCs, HO-1/BM-MSCs or normal saline (NS) injected through the dorsal penile vein. Transplanted liver tissues at 0, 1, 3, 5, 7, 10 and 14 days following transplantation were acquired for further analysis. The results indicated that the expression of autophagy-related proteins LC3 and Beclin-1 increased, the levels of ERK and p-ERK increased, and the levels of mammalian target of rapamycin (mTOR) and p-mTOR decreased in the HO-1/BM-MSCs. These observations indicated that autophagy is involved in the protective effects of HO-1/BM-MSCs on liver grafts following RSLT, possibly via upregulation of autophagy-related proteins through the ERK/mTOR signaling pathway.

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TERT alleviates irradiation-induced late rectal injury by reducing hypoxia-induced ROS levels through the activation of NF-κB and autophagy

Cited by 17 publications

References 37 publications

The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

Insulin-like growth factor 1 receptor-mediated cell survival in hypoxia depends on the promotion of autophagy via suppression of the PI3K/Akt/mTOR signaling pathway

Protective effects of heme oxygenase-1-transduced bone marrow-derived mesenchymal stem cells on reduced-size liver transplantation: Role of autophagy regulated by the ERK/mTOR signaling pathway

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