HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells

Li, Peng; He, Qing; Li, Xiaoyan; Shuai, Lanjun; Chen, Hạixia; Li, Yongzhen; Yi, Zhao

doi:10.3892/mmr.2016.5247

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…NRK-52e cells, in high glucose concentrations, will cause the initiation of epithelial-mesenchymal transition due to lipid deposition [22]. EMT is a key and basic biological behavior of cells, and it is also a key mechanism of renal interstitial fibrosis [23,24]. When the cells or organs undergo fibrosis, the connective tissues increase, and parenchymal cells are reduced.…”

Section: Discussionmentioning

confidence: 99%

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36

et al. 2021

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Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial–mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 μmol/L sodium oleate were given 10 μmoL/L moracin-P-2″-O-β-d-glucopyranoside (Y-1), moracin-P-3′-O-β-d-glucopyranoside (Y-2), moracin-P-3′-O-α-l-arabinopyranoside (Y-3), and moracin-P-3′-O-[β-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1β), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-β, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-β-d-glucopyranoside and moracin-P-3′-O-β-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.

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Section: Discussionmentioning

confidence: 99%

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36

et al. 2021

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“…Homeobox protein Hox-A13 (HOXA13), a transcriptional factor encoded by a homeobox gene, can bind to the promoter region of USAG-1 and negatively modulating expression (47). A recent study revealed that albumin could significantly inhibit HOXA13 expression in time- and dose-dependent manners in HKC renal tubular epithelial cells, and the upregulation of HOXA13 could exert a beneficial effect in albumin-induced EMT in HKC cells (48). Additionally, it has been reported that EMT-induced by albumin in HK-2 cells is directly mediated by the production of reactive oxygen species (ROS) (49,50).…”

Section: Discussionmentioning

confidence: 99%

Febuxostat inhibits TGF‑β1‑induced epithelial‑mesenchymal transition via downregulation of USAG‑1 expression in Madin‑Darby canine kidney cells in�vitro

Zhu²,

Zhang

et al. 2019

Mol Med Report

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Our previous study demonstrated that febuxostat, a xanthine oxidase inhibitor, can alleviate kidney dysfunction and ameliorate renal tubulointerstitial fibrosis in a rat unilateral ureteral obstruction (UUO) model; however, the underlying mechanisms remain unknown. Increasing evidence has revealed that epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating the progression of renal tubulointerstitial fibrosis in chronic kidney disease (CKD). Uterine sensitization-associated gene-1 (USAG-1), a kidney-specific bone morphogenetic protein antagonist, is involved in the development of numerous types of CKDs. The present study aimed to investigate the role of febuxostat in the process of EMT in Madin-Darby canine kidney (MDCK) cells in vitro . Western blotting, reverse transcription-semiquantitative polymerase chain reaction analysis and immunofluorescence staining were used to evaluate the expression levels of bone morphogenetic protein 7, USAG-1, α-smooth muscle actin (α-SMA) and E-cadherin, respectively. The results demonstrated that the expression of USAG-1 and α-SMA increased, and that of E-cadherin decreased significantly in MDCK cells following treatment with transforming growth factor-β1 (TGF-β1). The application of small interfering RNA-USAG-1 potently inhibited TGF-β1-induced EMT. Subsequently, the effects of febuxostat on TGF-β1-induced EMT was investigated. The results demonstrated that febuxostat downregulated the expression of USAG-1, and reversed TGF-β1-induced EMT in MDCK cells. Furthermore, pretreatment with febuxostat significantly restored the decreased expression levels of phosphorylated Smad1/5/8 induced by TGF-β1 in MDCK cells. The results of the present study suggested that USAG-1 may be involved in the EMT process of MDCK cells induced by TGF-β1, and febuxostat inhibited EMT by activating the Smad1/5/8 signaling pathway via downregulating the expression of USAG-1 in MDCK cells.

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“…In addition, some research suggests that the expression of HOX genes is closely related to EMT. For example, HOXA13 exerts a beneficial effect in albumin‐induced EMT via the glucocorticoid receptor pathway in human renal tubular epithelial cells, and HOXB13 overexpression is correlated with the aberrant expression of EMT markers in pancreatic carcinoma . In the current study, Snail and E‐cadherin, markers of EMT, were deregulated and upregulated in cells with low expression, respectively (i.e.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

et al. 2018

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BackgroundChemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance.MethodsOne hundred thirty‐one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half‐maximal inhibitory concentration of cisplatin, apoptosis, and epithelial‐to‐mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit‐8, flow cytometry, and transwell analysis.ResultsThe median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half‐maximal inhibitory concentration of cisplatin (P < 0.05), increased cisplatin‐induced apoptosis (P < 0.05), and decreased EMT (P < 0.05) compared with high HOXA13 expressed cells. In low HOXA13 expressed cells, cleaved caspase‐3 and cleaved PARP expression induced by cisplatin increased, while expression of E‐cadherin and Snail protein, markers of EMT, was upregulated and downregulated, respectively. EMT decreased in low HOXA13 expressed cells.ConclusionHigh HOXA13 expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy. HOXA13 increased cisplatin‐resistance and promoted EMT in ESCC cells.

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HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells

Cited by 4 publications

References 18 publications

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36

Febuxostat inhibits TGF‑β1‑induced epithelial‑mesenchymal transition via downregulation of USAG‑1 expression in Madin‑Darby canine kidney cells in�vitro

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

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