CELL BIOCHEMISTRY AND BIOPHYSICS
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2024
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IF 1.8
Yin Lifen,Wang Xiao
Oral submucous fibrosis (OSF) is a precancerous lesion of the oral cavity. Areca nut consumption can cause OSF through sustained activation of buccal mucosal fibroblasts (BMFs). This study explored the effect of curcumin on arecoline-induced BMF activation and its mechanism of action. BMFs were isolated and identified by immunofluorescence detection of fibroblast surface markers vimentin and S100A4. After transfection with FOSL1- or MAPK8-related vectors, BMFs were activated by arecoline and treated with curcumin. Scratch and transwell assays were performed to detect cell migration. ChIP and luciferase reporter assays were conducted to detect the binding of FOSL1 to the MAPK8 promoter. RT-qPCR was used to detect FOSL1 and MAPK8 mRNA expression. Western blotting was used to detect FOSL1, MAPK8, COL1A1, α-SMA, Smad2, and p-Smad2 proteins. Curcumin treatment inhibited arecoline-induced fibroblast migration, reduced the expression of myofibroblast markers COL1A1, α-SMA, and p-Smad2, and downregulated the expression of FOSL1 and MAPK8. FOSL1 or MAPK8 overexpression enhanced migration and increased COL1A1, α-SMA, and p-Smad2 expression in curcumin-treated cells. FOSL1 bound to the MAPK8 promoter and promoted MAPK8 expression. Simultaneous FOSL1 overexpression and MAPK8 knockdown, compared to FOSL1 overexpression, reduced cell migration and inhibited COL1A1, α-SMA, and p-Smad2 expression. In conclusion, curcumin targets FOSL1 to reduce MAPK8 expression, thereby suppressing arecoline-induced fibroblast activation.
研究领域:
药理学
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分子生物学
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肿瘤学
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牙医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
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2022
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IF 6.832
Mingming Ma,Qiao Luo,Lijing Fan,Weilong Li,Qiang Li,Yu Meng,Chen Yun,Hongwei Wu,Yongping Lu,Shuang Cui,Fanna Liu,Bo Hu,Baozhang Guan,Huanhuan Liu,Shengling Huang,Wenxue Liang,Stanislao Morgera,Bernhard Krämer,Shaodong Luan,Lianghong Yin,Berthold Hocher
Acute kidney injury (AKI) is a susceptible factor for chronic kidney disease (CKD). There is still a lack of effective prevention methods in clinical practice. This study investigated the protective effect of the urinary exosomes from premature infants on cisplatin-induced acute kidney injury. Here we isolated exosomes from the fresh urine of premature infants. A C57BL/6 mice model of cisplatin-induced acute kidney injury was given 100 ug urinary exosomes 24 hours after model establishment. The kidneys were collected for pathological examination and the evaluation of renal tubular damage and apoptosis. In the in vitro experiment, human renal cortex/proximal tubular cells (HK-2) were induced by cisplatin to assess the effect of the urine exosomes from premature infants. Exosome microRNA (miRNA) sequencing technology was applied to investigate the miRNAs enriched in exosomes and the dual-luciferase gene reporter system to examine the targeting relationship of the miRNA with target genes. The results indicated that the urinary exosomes could decrease the serum creatinine level and the apoptosis of renal tubular cells, and reduce mice mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes. It protected HK-2 cells from cisplatin-induced apoptosis by targeting and down-regulating the mitogen-activated protein kinase 8 (MAPK8). Together, our findings identified that the urinary exosomes derived from premature infants alleviated cisplatin-induced acute kidney injury and inhibited the apoptosis of HK-2 via miR-30a-5p, which could target MAPK8. These findings implied that urinary exosomes from premature infants riched in miR-30a-5p might become a potential treatment for AKI.
研究领域:
肾病学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2026
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IF 4.1
Jingchun Wang,Mingzheng Han,Jingling Yu,Bohao Chen,Shuaihao Guo,Ziqi Wu,Hai Huang,Zhaoxin Tang,Jianzhao Liao,Jianying Guo
Copper (Cu) exposure poses significant threats to renal health yet effective mitigation strategies remain scarce. Kaempferol (Kae) is a naturally occurring flavonoid with well-documented antioxidant and anti-apoptosis activities. Nevertheless, its protective effects in renal copper poisoning and the underlying molecular mechanisms have not been fully elucidated. This study integrated network toxicology, pharmacology, molecular docking, molecular dynamics simulation and a broiler model preliminarily revealed the mechanism of Kae alleviates Cu-induced nephrotoxicity (CuN). The potential targets of CuN scanned from Comparative Toxicogenomics Database (CTD), GeneCards database (GC) and the targets of Kae scanned from SwissTargetPrediction, PharmMapper database were used to perform GO and KEGG enrichment analysis. STRING and Cytoscape were employed to constructed PPI networks and locked on core targets. Molecular docking and dynamics simulations were used to investigate the binding affinity and stability of Kae with the core targets. A broiler model to further validate the impact of Kae on key signaling pathways. Notably, Kae effectively ameliorated histopathological damage caused by excess Cu and restored renal function ( P < 0.05). Network results revealed the involvement of apoptosis and MAPK signaling pathway, with Caspase-3 (CASP3) and Mitogen-activated protein kinase 8 (MAPK8) identified as core targets. In vivo experiments demonstrated that Cu significantly up-regulated the levels of Cleaved-CASP3 and phosphorylated MAPK8 and the expression of genes and proteins involved in promoting endogenous apoptosis ( P < 0.05), while Kae markedly reversed these effects and reduced TUNEL staining positive rate from 43.83% to approximately 12.84% ( P < 0.05). In summary, our findings demonstrate that Kae alleviates CuN by targeting the apoptotic process and the MAPK/JNK signaling axis, highlighting its potential as a natural therapeutic agent against heavy metal-induced nephrotoxicity in agricultural settings.
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Ting-Ting He,Xin Li,Jie-Zhi Ma,Yuan Yang,Shiye Zhu,Jianhua Zeng,Lin Luo,Yu-Long Yin,Lin-Ying Cao
Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Tingting Wang,Xiaoting Huang,Kefeng Zhai,Jialin Yu,Jiaxi Li,Hong Duan,Jinhong Liu,Zhuojian Lu,Jia Guo,Fei Li
Ethnopharmacological relevance Panax japonicus C. A. Meye (PJ) has unique effects on diseases by “qi” stagnation and blood stasis in ancient. Modern studies have shown that PJ can treat diabetic kidney disease (DKD) caused by deficiency and blood stasis. Aim of the study This study evaluated the potential effects of PJ on DKD, a microvascular complication, and investigated its possible mechanisms. Materials and methods In this study, the chemical constituents of PJ were analyzed by HPLC. In vivo studies, we constructed a diabetic mice model by HDF combined with STZ , then administered PJ to diabetic mice for 6 weeks. Blood lipid, BUN, 24h urine protein, and renal tissue HE staining were detected to comprehensively evaluate the protective effect of PJ on DKD. Metabolomics investigated the metabolic pathways influenced by PJ in the treatment of DKD. Moreover, the potential targets and signal pathways were investigated using network pharmacology . Finally, molecular docking predicts affinity of active compounds and core targets, and western blotting was used to detect core target expression levels. Results In vivo study, PJ can reduce hyperlipidemia , serum BUN, and 24-h urinary protein in diabetic mice, and protect the pathological changes in renal tissue. Metabolomics results showed that PJ had significant regulatory effect on unsaturated fatty acids , glycerophospholipid metabolism, and purine metabolism. Network pharmacology showed that MAPK1, MAPK8, Bcl-2, and Caspase 3 were the core targets in PJ against DKD. Molecular docking revealed that Bcl-2 and Caspase 3 have a strong affinity for Chikusetsusaponin Iva , Ginsenoside Rb1 , and Ginsenoside Rg1 . Moreover, when compared to the model group, the PJ group had higher levels of anti-apoptosis protein Bcl-2 and lower levels of pro-apoptosis protein Caspase 3. Conclusion PJ can reduce blood lipids, regulate the biosynthesis of unsaturated fatty acids and purine metabolism, thereby alleviating the renal injury of diabetic mice. Moreover, it can regulate the Bcl-2/caspase 3 apoptosis signaling pathway to prevent the apoptosis of renal cells and protect the renal function of diabetic mice.
研究领域:
药理学
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代谢组学
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糖尿病研究
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分子生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）