title: Modulation of LXR-α and the effector genes by Ascorbic acid and Statins in psoriatic keratinocytes.
abstract: Recent studies have revealed critical roles that nuclear receptors like LXR-α (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-α plays crucial role in keratinocyte proliferation and differentiation, it becomes imperative to dissect the pathways and role of LXR-α 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-α 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 β-galactosidase (β-gal) reporter plasmid assay in keratinocytes from clinically heathy subjects. Determination of relative levels of LXR-α,VDR and catalase in control versus treated cells upon activation of LXR-α 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 β-gal activity compared to the control. An increase of 55% in LXR-α 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.
authors.affiliation: Department of Dermatology, Postgraduate Institute of Medical Education & Research, Sector-12, Chandigarh, 160012, India, deeptisood@me.com.
authors.forename: Deepti
authors.initials: D
authors.lastname: Soodgupta
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaul
authors.forename: A J
authors.initials: AJ
authors.lastname: Kanwar
authors.forename: Davinder
authors.initials: D
authors.lastname: Parsad
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D000069059:Atorvastatin; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000096:biosynthesis* / Q000235:genetics; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D011758:Pyrroles; C003585:22-hydroxycholesterol; D000069059:Atorvastatin; D001205:Ascorbic Acid