Login Register Cart 0
Generic placeholder image

Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade

Author(s): Junjie Cao, Meifeng Xu, Longfei Zhu and Shengxiang Xiao*

Volume 24, Issue 13, 2023

Published on: 13 October, 2023

Page: [1055 - 1065] Pages: 11

DOI: 10.2174/0113894501243867230928115205

Price: $65

Abstract

Background: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown.

Methods: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application.

Results: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models.

Conclusion: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

« Previous Next »
Graphical Abstract

[1]
Leung AKC, Barankin B, Lam JM, Leong KF, Hon KL. Dermatology: How to manage acne vulgaris. Drugs Context 2021; 10: 1-18.
[http://dx.doi.org/10.7573/dic.2021-8-6] [PMID: 34691199]
[2]
Cao L, Zheng F, Ma P, et al. LC-APCI-MS-MS method for the tissue distribution of viaminate after oral administrations to rats. J Chromatogr Sci 2008; 46(8): 701-6.
[http://dx.doi.org/10.1093/chromsci/46.8.701] [PMID: 18796226]
[3]
Yin J, Ni KY, Shen Y, et al. Development and validation of a LC-MS/MS method for the determination of viaminate in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 856(1-2): 376-80.
[http://dx.doi.org/10.1016/j.jchromb.2007.06.033] [PMID: 17644497]
[4]
Cao J, Xu M, Zhu L, Xiao S. Viaminate ameliorates propionibacterium acnes-induced acne via inhibition of the TLR2/NF-κB and MAPK pathways in rats. Naunyn Schmiedebergs Arch Pharmacol 2023; 396(7): 1487-500.
[http://dx.doi.org/10.1007/s00210-022-02379-0] [PMID: 36757484]
[5]
Farrah G, Tan E. The use of oral antibiotics in treating acne vulgaris: A new approach. Dermatol Ther 2016; 29(5): 377-84.
[http://dx.doi.org/10.1111/dth.12370] [PMID: 27306750]
[6]
Kolar SL, Tsai CM, Torres J, Fan X, Li H, Liu GY. Propionibacterium acnes–induced immunopathology correlates with health and disease association. JCI Insight 2019; 4(5): e124687.
[http://dx.doi.org/10.1172/jci.insight.124687] [PMID: 30843879]
[7]
Wang Y, Zhang Z, Chen L, et al. Cathelicidin-BF, a snake cathelicidin-derived antimicrobial peptide, could be an excellent therapeutic agent for acne vulgaris. PLoS One 2011; 6(7): e22120.
[http://dx.doi.org/10.1371/journal.pone.0022120] [PMID: 21789223]
[8]
Hughes BR, Morris C, Cunliffe WJ, Leigh IM. Keratin expression in pilosebaceous epithelia in truncal skin of acne patients. Br J Dermatol 1996; 134(2): 247-56.
[http://dx.doi.org/10.1111/j.1365-2133.1996.tb07609.x] [PMID: 8746337]
[9]
Kurokawa I, Nakase K. Recent advances in understanding and managing acne. F1000 Res 2020; 9: 792.
[http://dx.doi.org/10.12688/f1000research.25588.1] [PMID: 32765835]
[10]
Rao X, Huang X, Zhou Z, Lin X. An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath 2013; 3(3): 71-85.
[PMID: 25558171]
[11]
Iotzova-Weiss G, Dziunycz PJ, Freiberger SN, et al. S100A8/A9 stimulates keratinocyte proliferation in the development of squamous cell carcinoma of the skin via the receptor for advanced glycation-end products. PLoS One 2015; 10(3): e0120971.
[http://dx.doi.org/10.1371/journal.pone.0120971] [PMID: 25811984]
[12]
Winston MH, Shalita AR. Acne vulgaris. Pathogenesis and treatment. Pediatr Clin North Am 1991; 38(4): 889-903.
[http://dx.doi.org/10.1016/S0031-3955(16)38158-5] [PMID: 1831256]
[13]
Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000 Res 2018; 7: 1953.
[http://dx.doi.org/10.12688/f1000research.15659.1] [PMID: 30613388]
[14]
Nabatanzi A, Mafuru M, Male M, et al. Feasibility study for the long-term management of refractory hyperkeratotic eczema with calcipotriol and betamethasone dipropionate (Daivobet®), viaminate and concomitant conventional therapies: a retrospective study. Clin Cosmet Investig Dermatol 2020; 13: 789-94.
[http://dx.doi.org/10.2147/CCID.S276148] [PMID: 33149651]
[15]
Pruenster M, Vogl T, Roth J, Sperandio M. S100A8/A9: From basic science to clinical application. Pharmacol Ther 2016; 167: 120-31.
[http://dx.doi.org/10.1016/j.pharmthera.2016.07.015] [PMID: 27492899]
[16]
Chan JK, Roth J, Oppenheim JJ, et al. Alarmins: Awaiting a clinical response. J Clin Invest 2012; 122(8): 2711-9.
[http://dx.doi.org/10.1172/JCI62423] [PMID: 22850880]
[17]
Korkmaz S, Fıçıcıoğlu SK. Calprotectin can play an inflammatory role in acne vulgaris. Postepy Dermatol Alergol 2018; 35(4): 397-9.
[http://dx.doi.org/10.5114/ada.2017.71286] [PMID: 30206454]
[18]
Lee Y, Jang S, Min JK, et al. S100A8 and S100A9 are messengers in the crosstalk between epidermis and dermis modulating a psoriatic milieu in human skin. Biochem Biophys Res Commun 2012; 423(4): 647-53.
[http://dx.doi.org/10.1016/j.bbrc.2012.05.162] [PMID: 22683330]
[19]
Xu Z, Cheng C, Kong R, et al. S100A8 and S100A9, both transcriptionally regulated by PU.1, promote epithelial-mesenchymal transformation (EMT) and invasive growth of dermal keratinocytes during scar formation post burn. Aging 2021; 13(11): 15523-37.
[http://dx.doi.org/10.18632/aging.203112] [PMID: 34099591]
[20]
Kim J, Shin YK, Kim KY. Promotion of keratinocyte proliferation by tracheloside through ERK1/2 stimulation. Evid Based Complement Alternat Med 2018; 2018: 1-5.
[http://dx.doi.org/10.1155/2018/4580627] [PMID: 30147732]
[21]
Wöll S, Windoffer R, Leube RE. p38 MAPK-dependent shaping of the keratin cytoskeleton in cultured cells. J Cell Biol 2007; 177(5): 795-807.
[http://dx.doi.org/10.1083/jcb.200703174] [PMID: 17535969]
[22]
Usuki S, Tamura N, Tamura T, et al. Konjac Ceramide (kCer)-mediated signal transduction of the sema3a pathway promotes hacat keratinocyte differentiation. Biology 2022; 11(1): 121.
[http://dx.doi.org/10.3390/biology11010121] [PMID: 35053118]
[23]
Meng X, Qiu L, Song H, Dang N. MAPK pathway involved in epidermal terminal differentiation of normal human epidermal keratinocytes. Open Med 2018; 13(1): 189-95.
[http://dx.doi.org/10.1515/med-2018-0029] [PMID: 29770357]
[24]
Jonak C, Mildner M, Klosner G, et al. The hsp27kD heat shock protein and p38-MAPK signaling are required for regular epidermal differentiation. J Dermatol Sci 2011; 61(1): 32-7.
[http://dx.doi.org/10.1016/j.jdermsci.2010.10.009] [PMID: 21081267]
[25]
Cursons J, Gao J, Hurley DG, et al. Regulation of ERK-MAPK signaling in human epidermis. BMC Syst Biol 2015; 9(1): 41.
[http://dx.doi.org/10.1186/s12918-015-0187-6] [PMID: 26209520]
[26]
Ghavami S, Rashedi I, Dattilo BM, et al. S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. J Leukoc Biol 2008; 83(6): 1484-92.
[http://dx.doi.org/10.1189/jlb.0607397] [PMID: 18339893]
[27]
Hayashi N, Kido J, Kido R, et al. Regulation of calprotectin expression by interleukin-1? and transforming growth factor-? in human gingival keratinocytes. J Periodontal Res 2007; 42(1): 1-7.
[http://dx.doi.org/10.1111/j.1600-0765.2005.00857.x] [PMID: 17214633]
[28]
Zhang H, Zhang J, Dong H. Fatal hepatotoxicity due to viaminate. Am J Med Sci 2018; 356(1): 84-6.
[http://dx.doi.org/10.1016/j.amjms.2018.01.001] [PMID: 30049333]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy