{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOVOL1 is a zinc‐finger transcription factor that plays a central role in establishing and maintaining the differentiated state of epithelial cells in the skin. In keratinocytes, OVOL1 regulates the expression of critical barrier proteins such as filaggrin, linking it to the pathobiology of atopic dermatitis and psoriasis. Immunolocalization studies demonstrate that in normal human skin, OVOL1 is predominantly expressed in the suprabasal epidermis, inner root sheath of hair follicles, mature sebocytes, and eccrine gland ducts, and genetic studies have further associated OVOL1 polymorphisms with a reduced risk of atopic dermatitis. Moreover, disruption of OVOL1 activity, including impaired nuclear translocation in disease settings, correlates with altered skin barrier functions and aberrant expression of filaggrin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its functions in the epidermis, OVOL1 regulates differentiation in distinct epithelial contexts. In the human placenta, OVOL1 is induced during trophoblast differentiation, where it facilitates the transition from progenitor cytotrophoblasts to the fused, hormone-producing syncytiotrophoblast by suppressing genes that maintain the undifferentiated state. In the hair follicle, OVOL1 acts in a mutually exclusive axis with OVOL2 to control cell proliferation and differentiation, implying its potential as a therapeutic target in hair disorders. Furthermore, comparative genomic analyses underscore that the conserved core of OVOL1, defined by its tetrad of C2H2 zinc fingers, marks an evolutionarily conserved regulator of epithelial identity, while its deregulation (for example via c-Myc upregulation) is linked to the progression from in situ lesions to invasive squamous cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, OVOL1 modulates cellular plasticity in broader pathological contexts. During somatic cell reprogramming, the induction of OVOL1 marks an alternative epithelial cell fate characterized by low proliferation and a specific mesenchymal‐to‐epithelial transition profile. In inflammatory skin conditions such as psoriasis and in breast cancer models, OVOL1 functions as a suppressor of epithelial–mesenchymal transition by inhibiting TGF‑β/SMAD signaling (in part by stabilizing SMAD7), thereby curtailing cell migration, invasion, and excessive inflammatory responses. These findings, together with emerging insights into the complex interplay between the epidermal microenvironment and host factors, underscore OVOL1’s multifaceted role in maintaining epithelial integrity and suggest its potential as a target in diverse clinical scenarios."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T Lepre, R Cascella, M Ragazzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of KIF3A, but not OVOL1 and ACTL9, with atopic eczema in Italian patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Dermatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjd.12178"}], "href": "https://doi.org/10.1111/bjd.12178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23278845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23278845"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chikage Mitoma, Takeshi Nakahara, Hiroshi Uchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fukuoka Igaku Zasshi (2014)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25509883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25509883"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhihua Kang, Qiao Li, Pan Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correlation of KIF3A and OVOL1, but not ACTL9, with atopic dermatitis in Chinese pediatric patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.06.068"}], "href": "https://doi.org/10.1016/j.gene.2015.06.068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26127003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26127003"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gaku Tsuji, Akiko Hashimoto-Hachiya, Mari Kiyomatsu-Oda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2017.322"}], "href": "https://doi.org/10.1038/cddis.2017.322"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28703805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28703805"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Aiat Shaban Hemida, Mostafa Ahmed Hammam, Aya Ahmed Swilam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of OVOL1 and Filaggrin immunohistochemical expression and clinical relevance in psoriasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diagn Pathol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13000-024-01491-4"}], "href": "https://doi.org/10.1186/s13000-024-01491-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38907248"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38907248"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Abhishek Kumar, Anita Bhandari, Rahul Sinha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular phylogeny of OVOL genes illustrates a conserved C2H2 zinc finger domain coupled by hypervariable unstructured regions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0039399"}], "href": "https://doi.org/10.1371/journal.pone.0039399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22737237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22737237"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Stephen J Renaud, Damayanti Chakraborty, Clifford W Mason, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OVO-like 1 regulates progenitor cell fate in human trophoblast development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1507397112"}], "href": "https://doi.org/10.1073/pnas.1507397112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26504231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26504231"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Takamichi Ito, Gaku Tsuji, Fumitaka Ohno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of the OVOL1-OVOL2 Axis in the Hair Bulb and in Pilomatricoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2015.12.013"}], "href": "https://doi.org/10.1016/j.ajpath.2015.12.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26873447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26873447"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Takamichi Ito, Gaku Tsuji, Fumitaka Ohno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2016.169"}], "href": "https://doi.org/10.1038/modpathol.2016.169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28339425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28339425"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Harunobu Kagawa, Ren Shimamoto, Shin-Il Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Reports (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stemcr.2018.12.008"}], "href": "https://doi.org/10.1016/j.stemcr.2018.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30639212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30639212"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Peng Sun, Remy Vu, Morgan Dragan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OVOL1 Regulates Psoriasis-Like Skin Inflammation and Epidermal Hyperplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2020.10.025"}], "href": "https://doi.org/10.1016/j.jid.2020.10.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33333123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33333123"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yukinobu Kutsuwada, Kazuha Yokota, Ken Yoshida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HLA-DPB1, NLRP10, OVOL1, and ABCC11 with the axillary microbiome in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdermsci.2022.01.003"}], "href": "https://doi.org/10.1016/j.jdermsci.2022.01.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35078690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35078690"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Chuannan Fan, Qian Wang, Gerard van der Zon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OVOL1 inhibits breast cancer cell invasion by enhancing the degradation of TGF-β type I receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Signal Transduct Target Ther (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41392-022-00944-w"}], "href": "https://doi.org/10.1038/s41392-022-00944-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35484112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35484112"}]}]}]}