Rhapontigenin inhibits TGF-β-mediated epithelial-mesenchymal transition via the PI3K/AKT/mTOR pathway and is not associated with HIF-1α degradation

Yeh, Yen-Hsiu; Wang, Shih‐Wei; Yeh, Yen-Cheng; Hsiao, Ho-Fu; Li, Tsai-Kun

doi:10.3892/or.2016.4664

Cited by 21 publications

(13 citation statements)

References 44 publications

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“…These results suggest that mTOR regulates EMT in HG conditions via the TGF-β1/PI3K/Akt signalling pathway. This is in agreement with a previous study, in which it was demonstrated that PI3K/Akt was activated during TGF-β1-induced EMT in cancer cells (44).…”

Section: Gsh (Mg/g Protein) T-sod (U/mg Protein) Mda (µMol/g Protein)supporting

confidence: 94%

ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

et al. 2018

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Oxidative stress has been reported to serve an important role in the development and progression of diabetic nephropathy (DN). Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells promotes renal fibrosis in DN, while the mechanism of reactive oxygen species (ROS)-mediated EMT is not fully understood. The aim of the present study was to investigate the effect of high glucose-induced ROS on the activation of the transforming growth factor (TGF)-β1/phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in a normal rat kidney tubular epithelial cell line (NRK-52E) and rats with type 1 diabetes. In vitro, high glucose-stimulated ROS production resulted in increased TGF-β1 expression as well as an increase in the Akt and mTOR phosphorylation ratio, resulting in EMT. When cells were pre-treated with ROS inhibitors, changes in TGF-β1, Akt and mTOR were significantly ameliorated. In vivo, diabetic rats experienced a significant decline in renal function and severe renal fibrosis compared with control rats at 8 weeks following streptozocin injection. Levels of malondialdehyde and TGF-β1/PI3K/Akt/mTOR pathway activation were increased in the renal cortex of rats with diabetes compared with the control rats. Furthermore, renal fibrosis was further aggravated in DN compared with the control rats. The results of the present study suggest that ROS serves an important role in mediating high glucose-induced EMT and inhibits activation of the TGF-β1/PI3K/Akt/mTOR pathway. ROS may therefore have potential as a treatment approach to prevent renal fibrosis in DN.

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Section: Gsh (Mg/g Protein) T-sod (U/mg Protein) Mda (µMol/g Protein)supporting

confidence: 94%

ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

et al. 2018

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“…We have also seen evidence of epithelial-mesenchymal transition (EMT) of amnion epithelial cells under oxidative stress conditions. TGF-β is a major mediator of EMT [ 61 – 65 ]. Molecular networks in CSE treated exosomes confirms that TGF-β mediated EMT may be functional in AECs under oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Amnion-Epithelial-Cell-Derived Exosomes Demonstrate Physiologic State of Cell under Oxidative Stress

et al. 2016

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At term, the signals of fetal maturity and feto-placental tissue aging prompt uterine readiness for delivery by transitioning quiescent myometrium to an active stage. It is still unclear how the signals reach the distant myometrium. Exosomes are a specific type of extracellular vesicle (EVs) that transport molecular signals between cells, and are released from a wide range of cells, including the maternal and fetal cells. In this study, we hypothesize that i) exosomes act as carriers of signals in utero-placental compartments and ii) exosomes reflect the physiologic status of the origin cells. The primary aims of this study were to determine exosomal contents in exosomes derived from primary amnion epithelial cells (AEC). We also determined the effect of oxidative stress on AEC derived exosomal cargo contents. AEC were isolated from amniotic membrane obtained from normal, term, not in labor placentae at delivery, and culture under standard conditions. Oxidative stress was induced using cigarette smoke extract for 48 hours. AEC-conditioned media were collected and exosomes isolated by differential centrifugations. Both growth conditions (normal and oxidative stress induced) produced cup shaped exosomes of around 50 nm, expressed exosomes enriched markers, such as CD9, CD63, CD81 and HSC70, embryonic stem cell marker Nanog, and contained similar amounts of cell free AEC DNA. Using confocal microscopy, the colocalization of histone (H) 3, heat shock protein (HSP) 70 and activated form of pro-senescence and term parturition associated marker p38 mitogen activated protein kinase (MAPK) (P-p38 MAPK) co-localized with exosome enrich marker CD9. HSP70 and P-p38 MAPK were significantly higher in exosomes from AEC grown under oxidative stress conditions than standard conditions (p<0.05). Finally, mass spectrometry and bioinformatics analysis identified 221 different proteins involved in immunomodulatory response and cell-to-cell communication. This study determined AEC exosome characteristics and their cargo reflected the physiologic status of the cell of origin and suggests that AEC-derived exosomal p38 MAPK plays a major role in determining the fate of pregnancy. Understanding the propagation of fetal signals and their mechanisms in normal term pregnancies can provide insights into pathologic activation of such signals associated with spontaneous preterm parturitions.

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“…Another limitation is that HFT differentiation was only analyzed using Oil Red O staining, not differentiation markers or fluorescence-activated cell sorting analysis. Additionally, previous studies have reported other potential molecular pathways that may be associated with the proliferation (33)(34)(35)(36)(37) and differentiation of HFTs, including the Wnt signal transduction pathway, forkhead box P1-mediated oxidative stress and epidermal growth factor receptor/extracellular signal-regulated kinases/AKT, c-Jun N-terminal kinases/c-Jun and TGF-β pathways (38). The present study only investigated the PI3K/AKT signaling pathway in HFTs.…”

Section: Discussionmentioning

confidence: 88%

Long non‑coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway

Cai

Zheng

et al. 2018

Mol Med Report

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Long non-coding RNAs (lncRNAs) are defined as non-coding transcripts (>200 nucleotides) that serve important roles in the proliferation and differentiation of stem cells. Hair follicle stem cells (HFTs) have multidirectional differentiation potential and are able to differentiate into skin, hair follicles and sebaceous glands, serving a role in skin wound healing. The aim of the present study was to analyze the regulatory role of lncRNA AK015322 (IncRNA5322) in HFTs and the potential mechanism of IncRNA5322‑mediated differentiation of HFTs. The results demonstrated that lncRNA5322 transfection promoted proliferation and differentiation in HFTs. It was identified that lncRNA5322 transfection upregulated the expression and phosphorylation of phosphoinositide 3‑kinase (PI3K) and protein kinase B (AKT) in HFTs. It was also observed that lncRNA5322 transfection upregulated microRNA (miR)‑21 and miR‑21 agonist (agomir‑21) eliminated lncRNA5322‑induced expression and phosphorylation of PI3K and AKT. The present study also demonstrated that agomir‑21 blocked IncRNA5322‑induced expression and phosphorylation of PI3K and AKT in HFTs. The results indicated that agomir‑21 transfection also suppressed the IncRNA5322‑induced proliferation and differentiation of HFTs. In conclusion, the results of the present study suggest that lncRNA5322 is able to promote the proliferation and differentiation of HFTs by targeting the miR‑21‑mediated PI3K‑AKT signaling pathway in HFTs.

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Rhapontigenin inhibits TGF-β-mediated epithelial-mesenchymal transition via the PI3K/AKT/mTOR pathway and is not associated with HIF-1α degradation

Cited by 21 publications

References 44 publications

ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

Amnion-Epithelial-Cell-Derived Exosomes Demonstrate Physiologic State of Cell under Oxidative Stress

Long non‑coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway

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