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Samuelov L, Bochner R, Magal L, et al. Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis. Exp Dermatol. 2021;doi: 10.1111/exd.14502.
Samuelov, L., Bochner, R., Magal, L., Malovitski, K., Sagiv, N., Nousbeck, J., Keren, A., Fuchs-Telem, D., Sarig, O., Gilhar, A., & Sprecher, E. (2021). Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis. Experimental dermatology, . https://doi.org/10.1111/exd.14502
Samuelov, Liat, et al. "Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis." Experimental dermatology vol. (2021). doi: https://doi.org/10.1111/exd.14502
Samuelov L, Bochner R, Magal L, Malovitski K, Sagiv N, Nousbeck J, Keren A, Fuchs-Telem D, Sarig O, Gilhar A, Sprecher E. Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis. Exp Dermatol. 2021 Nov 17; doi: 10.1111/exd.14502. Epub 2021 Nov 17. PMID: 34787924.
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Exp Dermatol. 2021 Nov 17; doi: 10.1111/exd.14502. Epub 2021 Nov 17.

Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis.

Experimental dermatology

Liat Samuelov, Ron Bochner, Lee Magal, Kiril Malovitski, Nadav Sagiv, Janna Nousbeck, Aviad Keren, Dana Fuchs-Telem, Ofer Sarig, Amos Gilhar, Eli Sprecher

Affiliations

  1. Division of Dermatology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
  2. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
  3. Skin Research Laboratory, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

PMID: 34787924 DOI: 10.1111/exd.14502

Abstract

BACKGROUND: Psoriasis is characterized by aberrant activation of several pro-inflammatory circuits as well as abnormal hyperproliferation and dysregulated apoptosis of keratinocytes (KCs). Most currently available therapeutic options primarily target psoriasis-associated immunological defects rather than epidermal abnormalities.

OBJECTIVE: To investigate the efficacy of the histone deacetylase (HDAC) inhibitor, Vorinostat, in targeting hyperproliferation and impaired apoptosis in psoriatic skin.

METHODS: Vorinostat effect was investigated in primary KCs cell cultures using cell cycle analysis by flow cytometry, apoptosis assays (Annexin V-FICH and caspase-3/7) and antibody arrays, qRT-PCR and immunohistochemistry. Vorinostat impact on clinical manifestations of psoriasis was investigated in a chimeric mouse model.

RESULTS: Vorinostat was found to inhibit KCs proliferation and to induce their differentiation and apoptosis. Using a chimeric mouse model, vorinostat was found to result in marked attenuation of a psoriasiform phenotype with a significant decrease in epidermal thickness and inhibition of epidermal proliferation.

CONCLUSIONS: Our results support the notion that vorinostat, a prototypic HDAC inhibitor, may be of potential use in the treatment of psoriasis and other hyperproliferative skin disorders.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords: Vorinostat; chimeric mice; histone deacetylase inhibitor; histone deacetylases; hyperproliferation; psoriasis

References

  1. Monteleone G, Pallone F, MacDonald TT, Chimenti S, Costanzo A. Psoriasis: from pathogenesis to novel therapeutic approaches. Clin Sci. 2011;120(1):1-11. - PubMed
  2. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263-271. - PubMed
  3. Boehm I. Apoptosis in physiological and pathological skin: implications for therapy. Curr Mol Med. 2006;6(4):375-394. - PubMed
  4. Chan JR, Blumenschein W, Murphy E, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med. 2006;203(12):2577-2587. - PubMed
  5. Raj D, Brash DE, Grossman D. Keratinocyte apoptosis in epidermal development and disease. J Invest Dermatol. 2006;126(2):243-257. - PubMed
  6. Ruckert R, Asadullah K, Seifert M, et al. Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis? J Immunol. 2000;165(4):2240-2250. - PubMed
  7. Tse WP, Cheng CH, Che CT, Lin ZX. Arsenic trioxide, arsenic pentoxide, and arsenic iodide inhibit human keratinocyte proliferation through the induction of apoptosis. J Pharmacol Exp Ther. 2008;326(2):388-394. - PubMed
  8. Pereira TM, Vieira AP, Fernandes JC, Sousa-Basto A. Cyclosporin A treatment in severe childhood psoriasis. J Eur Acad Dermatol Venereol. 2006;20(6):651-656. - PubMed
  9. Mrowietz U, Asadullah K. Dimethylfumarate for psoriasis: more than a dietary curiosity. Trends Mol Med. 2005;11(1):43-48. - PubMed
  10. Warren RB, Chalmers RJ, Griffiths CE, Menter A. Methotrexate for psoriasis in the era of biological therapy. Clin Exp Dermatol. 2008;33(5):551-554. - PubMed
  11. Kopp T, Karlhofer F, Szepfalusi Z, Schneeberger A, Stingl G, Tanew A. Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type. Br J Dermatol. 2004;151(4):912-916. - PubMed
  12. Holme SA, Anstey AV. Phototherapy and PUVA photochemotherapy in children. Photodermatol Photoimmunol Photomed. 2004;20(2):69-75. - PubMed
  13. Sanclemente G, Murphy R, Contreras J, Garcia H. Bonfill Cosp X. Anti-TNF agents for paediatric psoriasis. Cochrane Database Syst Rev. 11, CD010017. - PubMed
  14. Tsang V, Dvorakova V, Enright F, Murphy M, Gleeson C. Successful use of infliximab as first line treatment for severe childhood generalized pustular psoriasis. J Eur Acad Dermatol Venereol. 2016;30:e117-e119. - PubMed
  15. Luu M, Cordoro KM. The evolving role of biologics in the treatment of pediatric psoriasis. Skin Ther Lett. 2013;18(2):1-4. - PubMed
  16. Fotiadou C, Lazaridou E, Giannopoulou C, Ioannides D. Ustekinumab for the treatment of an adolescent patient with recalcitrant plaque psoriasis. Eur J Dermatol. 2011;21(1):117-118. - PubMed
  17. Camela E, Ocampo-Garza SS, Cinelli E, Villani A, Fabbrocini G, Megna M. Therapeutic update of biologics and small molecules for scalp psoriasis: a systematic review. Dermatol Ther. 2021;34(2):e14857. - PubMed
  18. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997;389(6649):349-352. - PubMed
  19. Newbold A, Matthews GM, Bots M, et al. Molecular and biologic analysis of histone deacetylase inhibitors with diverse specificities. Mol Cancer Ther. 2013;12(12):2709-2721. - PubMed
  20. Seidel C, Schnekenburger M, Dicato M, Diederich M. Histone deacetylase modulators provided by mother nature. Genes Nutr. 2012;7(3):357-367. - PubMed
  21. Barneda-Zahonero B, Parra M. Histone deacetylases and cancer. Mol Oncol. 2012;6(6):579-589. - PubMed
  22. Gediya P, Parikh PK, Vyas VK, Ghate MD. Histone deacetylase 2: a potential therapeutic target for cancer and neurodegenerative disorders. Eur J Med Chem. 2021;216:113332. - PubMed
  23. Lourenço de Freitas N, Deberaldini MG, Gomes D, et al. Histone deacetylase inhibitors as therapeutic interventions on cervical cancer induced by human papillomavirus. Front Cell Dev Biol. 2021;8:592868. - PubMed
  24. Jenke R, Ressing N, Hansen FK, Aigner A, Buch T. Anticancer therapy with HDAC inhibitors: mechanism-based combination strategies and future perspectives. Cancers. 2021;13(4):634. - PubMed
  25. Zhuang J, Huo Q, Yang F, Xie N. Perspectives on the role of histone modification in breast cancer progression and the advanced technological tools to study epigenetic determinants of metastasis. Front Genet. 2020;11:603552. - PubMed
  26. Li G, Tian Y, Zhu WG. The roles of histone deacetylases and their inhibitors in cancer therapy. Front Cell Dev Biol. 2020;8:576946. - PubMed
  27. Verza FA, Das U, Fachin AL, Dimmock JR, Marins M. Roles of histone deacetylases and inhibitors in anticancer therapy. Cancers. 2020;12(6):1664. - PubMed
  28. LeBoeuf M, Terrell A, Trivedi S, et al. Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell. 2010;19(6):807-818. - PubMed
  29. Higashitsuji H, Higashitsuji H, Masuda T, Liu Y, Itoh K, Fujita J. Enhanced deacetylation of p53 by the anti-apoptotic protein HSCO in association with histone deacetylase 1. J Biol Chem. 2007;282(18):13716-13725. - PubMed
  30. Laurikkala J, Mikkola ML, James M, Tummers M, Mills AA, Thesleff I. p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development. 2006;133(8):1553-1563. - PubMed
  31. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res. 2007;5(10):981-989. - PubMed
  32. Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 2007;12(10):1247-1252. - PubMed
  33. Harrison SJ, Bishton M, Bates SE, et al. A focus on the preclinical development and clinical status of the histone deacetylase inhibitor, romidepsin (depsipeptide, Istodax((R))). Epigenomics. 2012;4(5):571-589. - PubMed
  34. Yasukawa K, Sawamura D, Goto M, Nakamura H, Shimizu H. Histone deacetylase inhibitors preferentially augment transient transgene expression in human dermal fibroblasts. Br J Dermatol. 2007;157(4):662-669. - PubMed
  35. Lemper M, Snykers S, Vanhaecke T, De Paepe K, Rogiers V. Current status of healthy human skin models: can histone deacetylase inhibitors potentially improve the present replacement models? Skin Pharmacol Physiol. 2014;27(1):36-46. - PubMed
  36. Zhang X-H, Qin-Ma, Wu H-P, et al. A review of progress in histone deacetylase 6 inhibitors research: structural specificity and functional diversity. J Med Chem. 2021;64(3):1362-1391. - PubMed
  37. von Knethen A, Heinicke U, Weigert A, Zacharowski K, Brune B. Histone deacetylation inhibitors as modulators of regulatory T cells. Int J Mol Sci. 2020;21(7):2356. - PubMed
  38. Shuttleworth SJ, Bailey SG, Townsend PA. Histone deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. Curr Drug Targets. 2010;11(11):1430-1438. - PubMed
  39. McLaughlin F, La Thangue NB. Histone deacetylase inhibitors in psoriasis therapy. Curr Drug Targets Inflamm Allergy. 2004;3(2):213-219. - PubMed
  40. Choudhary V, Olala LO, Kagha K, et al. Regulation of the glycerol transporter, aquaporin-3, by histone deacetylase-3 and p53 in keratinocytes. J Invest Dermatol. 2017;137(9):1935-1944. - PubMed
  41. Porcu P, Hudgens S, Horwitz S, et al. Quality of life effect of the anti-CCR4 monoclonal antibody mogamulizumab versus vorinostat in patients with cutaneous T-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2021;21(2):97-105. - PubMed
  42. Duvic M, Vu J. Update on the treatment of cutaneous T-cell lymphoma (CTCL): focus on vorinostat. Biologics. 2007;1(4):377-392. - PubMed
  43. Quinn DI, Tsao-Wei DD, Twardowski P, et al. Phase II study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid; SAHA) in recurrent or metastatic transitional cell carcinoma of the urothelium - an NCI-CTEP sponsored: California Cancer Consortium trial, NCI 6879. Invest New Drugs. 2021;39(3):812-820. - PubMed
  44. Janku F, Park H, Call SG, et al. Safety and efficacy of vorinostat plus sirolimus or everolimus in patients with relapsed refractory hodgkin lymphoma. Clin Cancer Res. 2020;26(21):5579-5587. - PubMed
  45. Gray SG. Epigenetic treatment of neurological disease. Epigenomics. 2011;3(4):431-450. - PubMed
  46. Vargas DM, De Bastiani MA, Parsons RB, Klamt F. Parkinson's disease master regulators on substantia nigra and frontal cortex and their use for drug repositioning. Mol Neurobiol. 2021;58(4):1517-1534. - PubMed
  47. Ververis K, Karagiannis TC. Potential non-oncological applications of histone deacetylase inhibitors. Am J Transl Res. 2011;3(5):454-467. - PubMed
  48. Feng Z, Yang Z, Gao X, Xue Y, Wang X. Resveratrol promotes HIV-1 Tat accumulation via AKT/FOXO1 signaling axis and potentiates vorinostat to antagonize HIV-1 latency. Curr HIV Res. 2021;19(3):238-247. - PubMed
  49. Lee J, Stephanie HR. Cancer epigenetics: mechanisms and crosstalk of a HDAC inhibitor, vorinostat. Chemotherapy. 2013;2(111):14934. - PubMed
  50. Gilhar A, Bergman R, Assay B, Ullmann Y, Etzioni A. The beneficial effect of blocking Kv1.3 in the psoriasiform SCID mouse model. J Invest Dermatol. 2011;131(1):118-124. - PubMed
  51. Alam MS, Getz M, Haldar K. Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model. Sci Transl Med. 2016;8(326):doi:10.1126/scitranslmed.aad9407 - PubMed
  52. Keshelava N, Houghton PJ, Morton CL, et al. Initial testing (stage 1) of vorinostat (SAHA) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2009;53(3):505-508. - PubMed
  53. Xu J, Shi J, Zhang J, Zhang Y. Vorinostat: a histone deacetylases (HDAC) inhibitor ameliorates traumatic brain injury by inducing iNOS/Nrf2/ARE pathway. Folia Neuropathol. 2018;56(3):179-186. - PubMed
  54. Buglio D, Georgakis GV, Hanabuchi S, et al. Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines. Blood. 2008;112(4):1424-1433. - PubMed
  55. Petruccelli LA, Dupere-Richer D, Pettersson F, Retrouvey H, Skoulikas S, Miller WH Jr. Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells. PLoS One. 2011;6(6):e20987. - PubMed
  56. Shi Y-K, Li Z-H, Han X-Q, et al. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances taxol-induced cell death in breast cancer. Cancer Chemother Pharmacol. 2010;66(6):1131-1140. - PubMed
  57. Xu J, Sampath D, Lang FF, et al. Vorinostat modulates cell cycle regulatory proteins in glioma cells and human glioma slice cultures. J Neurooncol. 2011;105(2):241-251. - PubMed
  58. Chen M-Y, Liao W-L, Lu Z, et al. Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes, apoptosis, G2/M arrest, and autophagy. Cancer. 2011;117(19):4424-4438. - PubMed
  59. Wang F, Zhang X, Xia P, Zhang L, Zhang Z. Enhancement of mRNA expression of survivin and human beta-defensin-3 in lesions of psoriasis vulgaris. Eur J Dermatol. 2016;26(1):28-33. - PubMed
  60. Altieri DC. New wirings in the survivin networks. Oncogene. 2008;27(48):6276-6284. - PubMed
  61. Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8(1):61-70. - PubMed
  62. Nousbeck J, Ishida-Yamamoto A, Bidder M, et al. IGFBP7 as a potential therapeutic target in psoriasis. J Invest Dermatol. 2011;131(8):1767-1770. - PubMed
  63. Gilhar A, Ullmann Y, Assy B, et al. Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes: induction of psoriasis by cells with natural killer receptors. J Invest Dermatol. 2002;119(2):384-391. - PubMed
  64. Garrido C, Tolstrup M, Søgaard OS, et al. In-vivo administration of histone deacetylase inhibitors does not impair natural killer cell function in HIV+ individuals. AIDS. 2019;33(4):605-613. - PubMed
  65. Rossi LE, Avila DE, Spallanzani RG, et al. Histone deacetylase inhibitors impair NK cell viability and effector functions through inhibition of activation and receptor expression. J Leukoc Biol. 2012;91(2):321-331. - PubMed
  66. Schmudde M, Friebe E, Sonnemann J, Beck JF, Broker BM. Histone deacetylase inhibitors prevent activation of tumour-reactive NK cells and T cells but do not interfere with their cytolytic effector functions. Cancer Lett. 2010;295(2):173-181. - PubMed
  67. Choo QY, Ho PC, Tanaka Y, Lin HS. Histone deacetylase inhibitors MS-275 and SAHA induced growth arrest and suppressed lipopolysaccharide-stimulated NF-kappaB p65 nuclear accumulation in human rheumatoid arthritis synovial fibroblastic E11 cells. Rheumatology. 2010;49(8):1447-1460. - PubMed
  68. Leoni F, Zaliani A, Bertolini G, et al. The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines. Proc Natl Acad Sci USA. 2002;99(5):2995-3000. - PubMed
  69. Reilly CM, Mishra N, Miller JM, et al. Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. J Immunol. 2004;173(6):4171-4178. - PubMed
  70. Bosisio D, Vulcano M, Del Prete A, et al. Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo. J Leukoc Biol. 2008;84(6):1540-1548. - PubMed
  71. Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013;34(4):174-181. - PubMed
  72. Raychaudhuri SP. Role of IL-17 in psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol. 2012;44(2):183-193. - PubMed
  73. Tao R, de Zoeten EF, Özkaynak E, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med. 2007;13(11):1299-1307. - PubMed
  74. Sugiyama H, Gyulai R, Toichi E, et al. Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol. 2005;174(1):164-173. - PubMed
  75. Zeng C, Tsoi LC, Gudjonsson JE. Dysregulated epigenetic modifications in psoriasis. Exp Dermatol. 2021;30(8):1156-1166. - PubMed
  76. Yi JZ, McGee JS. Epigenetic-modifying therapies: an emerging avenue for the treatment of inflammatory skin diseases. Exp Dermatol. 2021;30(8):1167-1176. - PubMed
  77. Zhang P, Su Y, Zhao M, Huang W, Lu Q. Abnormal histone modifications in PBMCs from patients with psoriasis vulgaris. Eur J Dermatol. 2011;21(4):552-557. - PubMed
  78. Zhang P, Su Y, Chen H, Zhao M, Lu Q. Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis vulgaris. J Dermatol Sci. 2010;60(1):40-42. - PubMed
  79. Ovejero-Benito MC, Reolid A, Sánchez-Jiménez P, et al. Histone modifications associated with biological drug response in moderate-to-severe psoriasis. Exp Dermatol. 2018;27(12):1361-1371. - PubMed
  80. Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood. 2008;112(6):2340-2352. - PubMed
  81. Bovenschen HJ, van de Kerkhof PC, van Erp PE, Woestenenk R, Joosten I, Koenen HJ. Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. J Invest Dermatol. 2011;131(9):1853-1860. - PubMed
  82. Fan X, Yan K, Meng Q, et al. Abnormal expression of SIRTs in psoriasis: decreased expression of SIRT 1-5 and increased expression of SIRT 6 and 7. Int J Mol Med. 2019;44(1):157-171. - PubMed
  83. Hwang Y-J, Na J-I, Byun S-Y, et al. Histone deacetylase 1 and sirtuin 1 expression in psoriatic skin: a comparison between guttate and plaque psoriasis. Life. 2020;10(9):157. - PubMed
  84. Lee JH, Kim JS, Park SY, Lee YJ. Resveratrol induces human keratinocyte damage via the activation of class III histone deacetylase, Sirt1. Oncol Rep. 2016;35(1):524-529. - PubMed
  85. Lee JH, Moon JH, Lee YJ, Park SY. SIRT1, a class III histone deacetylase, regulates LPS-induced inflammation in human keratinocytes and mediates the anti-inflammatory effects of Hinokitiol. J Invest Dermatol. 2017;137(6):1257-1266. - PubMed
  86. Xie S, Su Z, Zhang B, et al. SIRT1 activation ameliorates aldara-induced psoriasiform phenotype and histology in mice. J Invest Dermatol. 2015;135(7):1915-1918. - PubMed
  87. Thatikonda S, Pooladanda V, Sigalapalli DK, Godugu C. Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation. Cell Death Dis. 2020;11(1):21. - PubMed
  88. Tovar-Castillo LE, Cancino-Diaz JC, Garcia-Vazquez F, et al. Under-expression of VHL and over-expression of HDAC-1, HIF-1alpha, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis. Int J Dermatol. 2007;46(3):239-246. - PubMed
  89. Li J, Post M, Volk R, et al. PR39, a peptide regulator of angiogenesis. Nat Med. 2000;6(1):49-55. - PubMed
  90. Koczulla R, von Degenfeld G, Kupatt C, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111(11):1665-1672. - PubMed
  91. Wu J, Parungo C, Wu G, et al. PR39 inhibits apoptosis in hypoxic endothelial cells: role of inhibitor apoptosis protein-2. Circulation. 2004;109(13):1660-1667. - PubMed
  92. Krane JF, Gottlieb AB, Carter DM, Krueger JG. The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor. J Exp Med. 1992;175(4):1081-1090. - PubMed
  93. Sorensen OE, Cowland JB, Theilgaard-Monch K, Liu L, Ganz T, Borregaard N. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J Immunol. 2003;170(11):5583-5589. - PubMed
  94. Schnekenburger M, Peng L, Puga A. HDAC1 bound to the Cyp1a1 promoter blocks histone acetylation associated with Ah receptor-mediated trans-activation. Biochim Biophys Acta. 2007;1769(9-10):569-578. - PubMed
  95. Robertson ED, Weir L, Romanowska M, Leigh IM, Panteleyev AA. ARNT controls the expression of epidermal differentiation genes through HDAC- and EGFR-dependent pathways. J Cell Sci. 2012;125(Pt 14):3320-3332. - PubMed
  96. Choudhary V, Olala LO, Qin H, et al. Aquaporin-3 re-expression induces differentiation in a phospholipase D2-dependent manner in aquaporin-3-knockout mouse keratinocytes. J Invest Dermatol. 2015;135(2):499-507. - PubMed
  97. Nakahigashi K, Kabashima K, Ikoma A, Verkman AS, Miyachi Y, Hara-Chikuma M. Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia. J Invest Dermatol. 2011;131(4):865-873. - PubMed
  98. Serna A, Galán-Cobo A, Rodrigues C, et al. Functional inhibition of aquaporin-3 with a gold-based compound induces blockage of cell proliferation. J Cell Physiol. 2014;229(11):1787-1801. - PubMed
  99. Qin H, Zheng X, Zhong X, Shetty AK, Elias PM, Bollag WB. Aquaporin-3 in keratinocytes and skin: its role and interaction with phospholipase D2. Arch Biochem Biophys. 2011;508(2):138-143. - PubMed
  100. Lee Y, Je Y-J, Lee S-S, et al. Changes in transepidermal water loss and skin hydration according to expression of aquaporin-3 in psoriasis. Ann Dermatol. 2012;24(2):168-174. - PubMed
  101. Voss KE, Bollag RJ, Fussell N, By C, Sheehan DJ, Bollag WB. Abnormal aquaporin-3 protein expression in hyperproliferative skin disorders. Arch Dermatol Res. 2011;303(8):591-600. - PubMed

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