摘要
Recent studies have revealed critical roles that nuclear receptors like LXR-alpha (Liver X Receptor- alpha) plays as a class of post-transcriptional gene regulator in skin development and diseases. Keeping in view the fact that LXR-alpha plays crucial role in keratinocyte proliferation and differentiation, it becomes imperative to dissect the pathways and role of LXR-alpha genomics in the pathogenesis of psoriasis with ultimate aim to explore novel preventive/therapeutic strategies as treatment options. To explore the effects of agonists and activators of LXR-alpha on its own gene expression and the putative targets in psoriatic keratinocytes. Identification of promoter sequences for (vitamin D receptor) VDR and Catalase were done using in silico analysis followed by beta-galactosidase (beta-gal) reporter plasmid assay in keratinocytes from clinically heathy subjects. Determination of relative levels of LXR-alpha,VDR and catalase in control versus treated cells upon activation of LXR-alpha with Atorvastatin + 22R hydroxycholestrol and Ascorbic acid + 22R hydroxycholestrol was done by PCR and Cell Proliferation Assay. The cells transfected with the reporter plasmid element for VDR and catalase showed more than 5 and 4 fold increase respectively in the beta-gal activity compared to the control. An increase of 55 % in LXR-alpha gene expression at RNA level was observed in Atorvastatin + 22-R hydroxycholestrol compared to 24 % in Ascorbic acid + 22-ROH cholesterol. The expression of the VDR and Catalase was significantly increased in both treated keratinocytes compared to its normal counterpart.
- 出版日期2014-12
- 单位河北医科大学