Adiponectin Upregulates Filaggrin Expression via SIRT1-Mediated Signaling in Human Normal Keratinocytes
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Background: Filaggrin (FLG) is the major component of the epidermal granular layer and binds to and condenses the keratin cytoskeleton. FLG thus contributes to cell compaction and serves as a natural moisturizing factor by promoting unfolding and degradation into hygroscopic amino acids. Loss or downregulation of FLG has been shown to result in a weak stratum corneum, which causes water loss and increases the possibility of skin barrier-related seizure. Adiponectin (Acrp30) contributes to the functional recovery of somatic cells, including human normal epidermal keratinocytes (NHEKs). Objective: To investigate the effect of Acrp30 in FLG expression and identifying its signal transduction mechanism. Methods: Normal human keratinocytes were treated with Acrp30 and the levels of FLG were examined. Silent mating type information regulation 2 homolog (SIRT)-targeting siRNA and aryl hydrocarbon receptor nuclear translocator (ARNT)-targeting siRNA were used to identify the role of various signal transduction pathway components. Results: Acrp30 upregulated SIRT1 and ARNT expression in NHEKs, resulting in increased FLG expression. Treatment with both SIRT1-targeting siRNA and ARNT-targeting siRNA blocked Acrp30 stimulation and silenced FLG expression. Conclusion: Adiponectin upregulates FLG expression through a SIRT1-mediated pathway. Our results suggest that Acrp30 is a promising agent for skin barrier permeability improvement.
Abstract
Background: Filaggrin (FLG) is the major component of the epidermal granular layer and binds to and condenses the keratin cytoskeleton. FLG thus contributes to cell compaction and serves as a natural moisturizing factor by promoting unfolding and degradation into hygroscopic amino acids. Loss or downregulation of FLG has been shown to result in a weak stratum corneum, which causes water loss and increases the possibility of skin barrier-related seizure. Adiponectin (Acrp30) contributes to the functional recovery of somatic cells, including human normal epidermal keratinocytes (NHEKs). Objective: To investigate the effect of Acrp30 in FLG expression and identifying its signal transduction mechanism. Methods: Normal human keratinocytes were treated with Acrp30 and the levels of FLG were examined. Silent mating type information regulation 2 homolog (SIRT)-targeting siRNA and aryl hydrocarbon receptor nuclear translocator (ARNT)-targeting siRNA were used to identify the role of various signal transduction pathway components. Results: Acrp30 upregulated SIRT1 and ARNT expression in NHEKs, resulting in increased FLG expression. Treatment with both SIRT1-targeting siRNA and ARNT-targeting siRNA blocked Acrp30 stimulation and silenced FLG expression. Conclusion: Adiponectin upregulates FLG expression through a SIRT1-mediated pathway. Our results suggest that Acrp30 is a promising agent for skin barrier permeability improvement.
참고문헌 (25)
- Sandilands A, "Filaggrin in the frontline: role in skin barrier function and disease", J Cell Sci, 122, pp.1285~1294 (2009)
- Kezic S, "Natural moisturizing factor components in the stratum corneum as biomarkers of Filaggrin genotype: evaluation of minimally invasive methods", Br J Dermatol, 161, pp.1098~1104 (2009)
- Wong WJ, "Hypoxia-inducible factors regulate Filaggrin expression and epidermal barrier function", J Invest Dermatol, 135, pp.454~461 (2015)
- Ming M, "Loss of sirtuin 1 (SIRT1) disrupts skin barrier integrity and sensitizes mice to epicutaneous allergen challenge", J Allergy Clin Immunol, 135, pp.936.e4~945.e4 (2015)
- Kwon HS, "The ups and downs of SIRT1", Trends Biochem Sci, 33, pp.517~525 (2008)
- Guo X, "The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status", Sci Rep, 2, pp.640~ (2012)
- Chaudhary N, "Metabolic benefits from Sirt1 and Sirt1 activators", Curr Opin Clin Nutr Metab Care, 12, pp.431~437 (2009)
- Blander G, "SIRT1 promotes differentiation of normal human keratinocytes", J Invest Dermatol, 129, pp.41~49 (2009)
- Laemmle A, "Inhibition of SIRT1 impairs the accumulation and transcriptional activity of HIF-1α protein under hypoxic conditions", PLoS One, 7, pp.e33433~ (2012)
- Fu Y, "Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation", J Lipid Res, 46, pp.1369~1379 (2005)
- Jin T, "Fisetin up-regulates the expression of adiponectin in 3T3-L1adipocytes via the activation of silent mating type information regulation 2 homologue 1 (SIRT1)-deacetylase and peroxisome proliferator-activated receptors (PPARs)", J Agric Food Chem, 62, pp.10468~10474 (2014)
- Liu Q, "Activation of AMP-activated protein kinase signaling pathway by adiponectin and insulin in mouse adipocytes: requirement of acyl-CoA synthetases FATP1 and Acsl1 and association with an elevation in AMP", ATP ratio, 2010, pp.24, 4229~4239
- Cantó C, "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity", Nature, 458, pp.1056~1060 (2009)
- Fullerton MD, "SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol", Diabetes, 59, pp.551~553 (2010)
- Shen Z, "Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice", Am J Physiol Gastrointest Liver Physiol, 298, pp.G364~G374 (2010)
- Iwabu M, "Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK", SIRT1, 2010, pp.464, 1313~1319
- Kovács D, "Sebocytes differentially express and secrete adipokines", Exp Dermatol, 25, pp.194~199 (2016)
- Costa Cdos S, "Resveratrol upregulated SIRT1, FOXO1, and adiponectin and downregulated PPARγ1-3mRNA expression in human visceral adipocytes", Obes Surg, 21, pp.356~361 (2011)
- Naowaboot J, "Rutin stimulates adipocyte differentiation and adiponectin secretion in 3T3-L1adipocytes", J Med Assoc Thai, (98 Suppl 3), pp.S1~S6 (2015)
- Furue M, "Role of AhR", ARNT system in skin homeostasis, 2014, pp.306, 769~779
- van den Bogaard EH, "Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis", J Clin Invest, 123, pp.917~927 (2013)
- Denison MS, "Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals", Annu Rev Pharmacol Toxicol, 43, pp.309~334 (2003)
- Wu Z, "Resveratrol inhibition of human keratinocyte proliferation via SIRT1", ARNT, J Dermatol Sci, pp.2014, 75[DOI]
- Schäfer M, "Nrf2 links epidermal barrier function with antioxidant defense", EMBO Mol Med, 4, pp.364~379 (2012)
- Eun Joo Kim, "Genetic Polymorphism of FLG in Korean Ichthyosis Vulgaris Patients", Annals of Dermatology, 23(2), pp.170~176 (2011), 대한피부과학회