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http://dx.doi.org/10.4162/nrp.2022.16.1.1

Bitter taste receptors protect against skin aging by inhibiting cellular senescence and enhancing wound healing  

Chung, Min Gi (Department of Nutritional Science and Food Management, Ewha Womans University)
Kim, Yerin (Department of Nutritional Science and Food Management, Ewha Womans University)
Cha, Yeon Kyung (Interdisciplinary Program in Bioengineering, Seoul National University)
Park, Tai Hyun (Interdisciplinary Program in Bioengineering, Seoul National University)
Kim, Yuri (Department of Nutritional Science and Food Management, Ewha Womans University)
Publication Information
Nutrition Research and Practice / v.16, no.1, 2022 , pp. 1-13 More about this Journal
Abstract
BACKGROUND/OBJECTIVES: Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells. MATERIALS/METHODS: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. RESULTS: TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. CONCLUSIONS: Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.
Keywords
Taste; galactose; skin aging; wound healing; keratinocytes;
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1 Mouse Genome Informatics (MGI). MGI gene page for Tas2r114 [Internet]. [place unknown]: MGI; 2020 [cited 2020 October 3]. Available from: http://www.informatics.jax.org/marker/MGI:2681218.
2 Zhang Y, Wang J, Cheng X, Yi B, Zhang X, Li Q. Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway. Eur J Histochem 2015;59:2467.
3 Ye Y, Jia RR, Tang L, Chen F. In vivo antioxidant and anti-skin-aging activities of ethyl acetate extraction from idesia polycarpa defatted fruit residue in aging mice induced by D-galactose. Evid Based Complement Alternat Med 2014;2014:185716.
4 Kim Y, Kim E, Kim Y. l-histidine and l-carnosine accelerate wound healing via regulation of corticosterone and PI3K/Akt phosphorylation in d-galactose-induced aging models in vitro and in vivo. J Funct Foods 2019;58:227-37.   DOI
5 Montesinos MC, Gadangi P, Longaker M, Sung J, Levine J, Nilsen D, Reibman J, Li M, Jiang CK, Hirschhorn R, Recht PA, Ostad E, Levin RI, Cronstein BN. Wound healing is accelerated by agonists of adenosine A2 (G α s-linked) receptors. J Exp Med 1997;186:1615-20.   DOI
6 Braun M, Lelieur K, Kietzmann M. Purinergic substances promote murine keratinocyte proliferation and enhance impaired wound healing in mice. Wound Repair Regen 2006;14:152-61.   DOI
7 Zhu H, Liu L, Ren L, Ma J, Hu S, Zhu Z, Zhao X, Shi C, Wang X, Zhang C, Gu M, Li X. Systematic prediction of the biological functions of TAS2R10 using positive co-expression analysis. Exp Ther Med 2020;19:1733-8.
8 Li YF, Ouyang SH, Tu LF, Wang X, Yuan WL, Wang GE, Wu YP, Duan WJ, Yu HM, Fang ZZ, Kurihara H, Zhang Y, He RR. Caffeine protects skin from oxidative stress-induced senescence through the activation of autophagy. Theranostics 2018;8:5713-30.   DOI
9 Shil A, Olusanya O, Ghufoor Z, Forson B, Marks J, Chichger H. Artificial sweeteners disrupt tight junctions and barrier function in the intestinal epithelium through activation of the sweet taste receptor, T1R3. Nutrients 2020;12:1862.   DOI
10 Wauson EM, Zaganjor E, Lee AY, Guerra ML, Ghosh AB, Bookout AL, Chambers CP, Jivan A, McGlynn K, Hutchison MR, Deberardinis RJ, Cobb MH. The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Mol Cell 2012;47:851-62.   DOI
11 Wang ZL, Chen LB, Qiu Z, Chen XB, Liu Y, Li J, Wang L, Wang YP. Ginsenoside Rg1 ameliorates testicular senescence changes in D-gal-induced aging mice via anti-inflammatory and antioxidative mechanisms. Mol Med Rep 2018;17:6269-76.
12 Li H, Zheng L, Chen C, Liu X, Zhang W. Brain senescence caused by elevated levels of reactive metabolite methylglyoxal on D-galactose-induced aging mice. Front Neurosci 2019;13:1004.   DOI
13 Xu C, Huang X, Tong Y, Feng X, Wang Y, Wang C, Jiang Y. Icariin modulates the sirtuin/NF-κB pathway and exerts anti-aging effects in human lung fibroblasts. Mol Med Rep 2020;22:3833-9.
14 Van Putte L, De Schrijver S, Moortgat P. The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review. Scars Burn Heal 2016;2:2059513116676828.   DOI
15 Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 2003;112:293-301.   DOI
16 Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses 2010;35:157-70.   DOI
17 Zhao P, Sui BD, Liu N, Lv YJ, Zheng CX, Lu YB, Huang WT, Zhou CH, Chen J, Pang DL, Fei DD, Xuan K, Hu CH, Jin Y. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application. Aging Cell 2017;16:1083-93.   DOI
18 Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol 2015;44-46:247-54.   DOI
19 Chen P, Chen F, Lei J, Li Q, Zhou B. Activation of the miR-34a-mediated SIRT1/mTOR signaling pathway by urolithin A attenuates D-galactose-induced brain aging in mice. Neurotherapeutics 2019;16:1269-82.   DOI
20 Liu Z, Hu GD, Luo XB, Yin B, Shu B, Guan JZ, Jia CY. Potential of bone marrow mesenchymal stem cells in rejuvenation of the aged skin of rats. Biomed Rep 2017;6:279-84.   DOI
21 Behrens M, Brockhoff A, Batram C, Kuhn C, Appendino G, Meyerhof W. The human bitter taste receptor hTAS2R50 is activated by the two natural bitter terpenoids andrographolide and amarogentin. J Agric Food Chem 2009;57:9860-6.   DOI
22 Seo Y, Kim YS, Lee KE, Park TH, Kim Y. Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells. PLoS One 2017;12:e0176851.   DOI
23 Carey RM, Adappa ND, Palmer JN, Lee RJ, Cohen NA. Taste receptors: regulators of sinonasal innate immunity. Laryngoscope Investig Otolaryngol 2016;1:88-95.   DOI
24 Campa D, De Rango F, Carrai M, Crocco P, Montesanto A, Canzian F, Rose G, Rizzato C, Passarino G, Barale R. Bitter taste receptor polymorphisms and human aging. PLoS One 2012;7:e45232.   DOI
25 Zhai KF, Duan H, Khan GJ, Xu H, Han FK, Cao WG, Gao GZ, Shan LL, Wei ZJ. Salicin from Alangium chinense ameliorates rheumatoid arthritis by modulating the Nrf2-HO-1-ROS pathways. J Agric Food Chem 2018;66:6073-82.   DOI
26 Grassin-Delyle S, Salvator H, Mantov N, Abrial C, Brollo M, Faisy C, Naline E, Couderc LJ, Devillier P. Bitter taste receptors (TAS2Rs) in human lung macrophages: receptor expression and inhibitory effects of TAS2R agonists. Front Physiol 2019;10:1267.   DOI
27 Shaw L, Mansfield C, Colquitt L, Lin C, Ferreira J, Emmetsberger J, Reed DR. Personalized expression of bitter 'taste' receptors in human skin. PLoS One 2018;13:e0205322.   DOI
28 Chen J, Li Y, Zhu Q, Li T, Lu H, Wei N, Huang Y, Shi R, Ma X, Wang X, Sheng J. Anti-skin-aging effect of epigallocatechin gallate by regulating epidermal growth factor receptor pathway on aging mouse model induced by D-galactose. Mech Ageing Dev 2017;164:1-7.   DOI
29 Xu H, Gan C, Gao Z, Huang Y, Wu S, Zhang D, Wang X, Sheng J. Caffeine targets SIRT3 to enhance SOD2 activity in mitochondria. Front Cell Dev Biol 2020;8:822.   DOI
30 Mazumder A, Dwivedi A, du Preez JL, du Plessis J. In vitro wound healing and cytotoxic effects of sinigrinphytosome complex. Int J Pharm 2016;498:283-93.   DOI
31 Disasa D, Cheng L, Manzoor M, Liu Q, Wang Y, Xiang L, Qi J. Amarogentin from Gentiana rigescens Franch exhibits antiaging and neuroprotective effects through antioxidative stress. Oxid Med Cell Longev 2020;2020:3184019.
32 Pronin AN, Xu H, Tang H, Zhang L, Li Q, Li X. Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin. Curr Biol 2007;17:1403-8.   DOI
33 Zhong J, Wang F, Wang Z, Shen C, Zheng Y, Ma F, Zhu T, Chen L, Tang Q, Zhu J. Aloin attenuates cognitive impairment and inflammation induced by d-galactose via down-regulating ERK, p38 and NF-κB signaling pathway. Int Immunopharmacol 2019;72:48-54.   DOI
34 Guo F, Wu R, Xu J. Salicin prevents TNF-α-induced cellular senescence in human umbilical vein endothelial cells (HUVECs). Artif Cells Nanomed Biotechnol 2019;47:2618-23.   DOI
35 Tran TA, Ho MT, Song YW, Cho M, Cho SK. Camphor induces proliferative and anti-senescence activities in human primary dermal fibroblasts and inhibits UV-induced wrinkle formation in mouse skin. Phytother Res 2015;29:1917-25.   DOI
36 Lee NY, Kim Y, Kim YS, Shin JH, Rubin LP, Kim Y. β-Carotene exerts anti-colon cancer effects by regulating M2 macrophages and activated fibroblasts. J Nutr Biochem 2020;82:108402.   DOI
37 Eppig JT. Mouse genome informatics (MGI) resource: genetic, genomic, and biological knowledgebase for the laboratory mouse. ILAR J 2017;58:17-41.   DOI
38 Lee HJ, Hwang E, Park B, Zhang M, Sun ZW, Lee DG, Park SY, Yi TH. Methanol extract of bitter melon alleviates UVB-induced MMPs expression via MAP kinase and AP-1 signaling in human dermal fibroblasts in vitro. Phytother Res 2016;30:1519-26.   DOI
39 Apraj VD, Pandita NS. Evaluation of skin anti-aging potential of Citrus reticulata blanco peel. Pharmacognosy Res 2016;8:160-8.   DOI
40 Chen WM, Chiang JC, Lin YC, Lin YN, Chuang PY, Chang YC, Chen CC, Wu KY, Hsieh JC, Chen SK, Huang WP, Chen BP, Lee H. Lysophosphatidic acid receptor LPA3 prevents oxidative stress and cellular senescence in Hutchinson-Gilford progeria syndrome. Aging Cell 2020;19:e13064.   DOI
41 Mouse Genome Informatics (MGI). MGI homepage [Internet]. [place unknown]: MGI; 2020 [cited 2020 October 3]. Available from: http://www.informatics.jax.org.
42 Mouse Genome Informatics (MGI). MGI gene page for Tas2r118 [Internet]. [place unknown]: MGI; 2020 [cited 2020 October 3]. Available from: http://www.informatics.jax.org/marker/MGI:2681247.
43 Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Soderhall C, Pulkkinen V, Pedroletti C, Daham K, Kupczyk M, Dahlen B, Kere J, Dahlen SE, Hedlin G, Melen E. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J 2013;42:65-78.   DOI
44 Farage MA, Miller KW, Elsner P, Maibach HI. Characteristics of the aging skin. Adv Wound Care (New Rochelle) 2013;2:5-10.   DOI
45 Cosgrove MC, Franco OH, Granger SP, Murray PG, Mayes AE. Dietary nutrient intakes and skin-aging appearance among middle-aged American women. Am J Clin Nutr 2007;86:1225-31.   DOI
46 Li T, Yang S, She X, Yan Q, Zhang P, Zhu H, Wang F, Luo X, Sun X. Modulation of α-adrenoceptor signalling protects photoreceptors after retinal detachment by inhibiting oxidative stress and inflammation. Br J Pharmacol 2019;176:801-13.   DOI
47 Song X, Bao M, Li D, Li YM. Advanced glycation in D-galactose induced mouse aging model. Mech Ageing Dev 1999;108:239-51.   DOI
48 Melis M, Errigo A, Crnjar R, Pes GM, Tomassini Barbarossa I. TAS2R38 bitter taste receptor and attainment of exceptional longevity. Sci Rep 2019;9:18047.   DOI
49 Barriere G, Fici P, Gallerani G, Fabbri F, Rigaud M. Epithelial mesenchymal transition: a double-edged sword. Clin Transl Med 2015;4:14.   DOI