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.

Role of Vitamin C in Skin Aging Mechanism-A Narrative Review

“…The review also covered the role of vitamin C in inhibiting melanogenesis by interacting with copper ions in the tyrosinase enzyme, thus reducing melanin production (28)(29)(30)(31). Furthermore, the therapeutic applications of vitamin C in treating various skin conditions, such as acne, atopic dermatitis, and hyperpigmentation, were explored (32)(33)(34)(35)(36)(37)(38). This review aimed to provide a comprehensive understanding of the multifaceted role of vitamin C in skin health and aging, drawing on the latest scientific evidence to inform future research and clinical practices.…”

“…In acne treatment, VITC, in combination with clarithromycin and zinc, has demonstrated efficacy in reducing inflammation and improving skin health. VITC is also utilized in microneedling procedures to minimize acne scars and is frequently incorporated into treatments for allergic skin conditions (32)(33)(34)(35)(36)(37)(38). The diverse applications of VITC in dermatology highlight its significance as a potent anti-aging and therapeutic agent.…”

“…Inhibitory effects on melanogenesis were observed, with vitamin C reducing melanin synthesis by 25% (Shimada et al, 2009). Additionally, therapeutic benefits were noted in treating acne, psoriasis, and hyperpigmentation, with a 40% improvement in acne scars (Chawla, 2014) and a 35% reduction in psoriasis symptoms (Soodgupta et al, 2014). Conclusion: Vitamin C plays a crucial role in maintaining skin health and combating aging through various mechanisms, including enhancing collagen synthesis, providing antioxidant protection, inhibiting melanogenesis, and treating skin diseases.…”

Role of Vitamin C in Skin Diseases

“…Skin pretreated with vitamin C can inhibit the allergic reaction induced by p -phenylenediamine ( Coenraads et al, 2016 ). More interestingly, in an experimental study on the role of LXR-a (liver X receptor alpha) in the pathogenesis of psoriasis, Soodgupta et al (2014) demonstrated that ascorbic acid and atorvastatin combined with 22- r -hydroxycholine returned female hormone-treated psoriatic keratinocytes to normal. Collagen is an important component in the connective tissue of the basement membrane and capillary vessels, and vitamin C is essential for collagen synthesis.…”

Roles of miRNA-24 in regulating endothelial nitric oxide synthase expression and vascular endothelial cell proliferation

“…We speculated that eNOS mRNA might be one of the targets of miRNA-24. Through bioinformatic prediction [13], we found that the sequence 5 0 -UGAGCCA -3 0 at 119-125 bases of eNOS 3 0 UTR (Genbank accession NM_001160111) was matched to the sequence 5 0 -UGGCUCA -3 0 within miRNA-24. In order to investigate if eNOS is a target gene of miRNA-24, we constructed luciferase reporter plasmids that contain the wt (5 0 -UGAGCCA-3 0 , pGL3-eNOS-wt) or mutant (5 0 -UCUCCCA-3 0 , pGL3-eNOS-mut) segment of eNOS b Anti-miRNA-24 group.…”