Molecular Mechanism of Arecoline-Induced Hypertrophy and Fibrosis in Proximal Renal Tubular Cells
| Autor: | Wan-Ting Ho, 何琬婷 |
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| Rok vydání: | 2012 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 100 There are over 200-600 million people who has the habit of chewing betal nuts worldwide and the prevalence rate of BQ chewing is about 10% in Taiwan. Betel quid chewing not only leads to oral, pharyngeal and esophageal cancers but also is associated with liver cirrhosis and hepatocellular carcinoma (HCC). Arecoline is the most abundant alkaloid in betel quid and is cytotoxic, genotoxic, mutagenic and tumorigenic to various kinds of cells. Betel nut chewing is also associated with metabolic symdrome, cardiovascular disease and chronic kidney disease. On the other side, heat shock factor 1 (HSF1) protects cells from stresses including anti-inflammatory, anti-oxidant, glucose tolerance and insulin resistant effects. Therefore, the mechanism of how arecoline affects kidney tubular epithelium cells (LLC-PK1) and the role of HSF1 in arecoline-induced effects on LLC-PK1 cells were studied. We found that arecoline inhibited LLC-PK1 cell growth in a dose-dependent and time-dependent manner. Additionally, arecoline induced LLC-PK1 cell hypertrophy. Arecoline also induced LLC-PK1 cell fibrosis by upregulating fibronectin, Collagen IV, Collagen I and plasminogen activator inhibitor- 1 (PAI-1) protein expression. Moreover, decreased of cyclin D1, cyclinE and increased of p21 waf1/cip1 protein expression can be found in arecoline-treated LLC-PK1 cells. We transfected phTH5 (TGF-beta promoter luciferase plasmid) to find out that arecoline activates JNK1/2 to induce TGF-??. We founf that JNK1/2 inhibitor (SP600125) attenuated arecoline-induced fibronectin, Collagen IV, Collagen I and PAI-1 while decreasing c-Jun and cycloxygenase-2 (COX2) expression in arecoline-treated cells. We found that arecoline decreased HSF1 protein expression. Thus, we transfected HSF1 overexpression plasmid to investigate the role of HSF1. We found that HSF1 overexpression attetuated arecoline-induced COX2 expression. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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