دورية أكاديمية
أعرض في EDS

HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis.

التفاصيل البيبلوغرافية
العنوان: HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis.
المؤلفون: Zhu X; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Xu M; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Millar SE; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Electronic address: sarah.millar@mssm.edu.
المصدر: The ocular surface [Ocul Surf] 2024 Jul; Vol. 33, pp. 39-49. Date of Electronic Publication: 2024 Apr 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101156063 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1937-5913 (Electronic) Linking ISSN: 15420124 NLM ISO Abbreviation: Ocul Surf Subsets: MEDLINE
أسماء مطبوعة: Publication: 2012- : [Philadelphia, PA] : Elsevier Inc.
Original Publication: New York, N.Y. : Ethis Communications, [c2003]-
مواضيع طبية MeSH: Meibomian Glands*/metabolism , Meibomian Glands*/pathology , Histone Deacetylase 1*/metabolism , Histone Deacetylase 1*/genetics , Homeostasis*/physiology , Histone Deacetylases*/metabolism , Histone Deacetylases*/genetics , Histone Deacetylase 2*/metabolism , Histone Deacetylase 2*/genetics , Apoptosis*, Animals ; Mice ; Cell Proliferation/physiology ; In Situ Nick-End Labeling ; In Situ Hybridization ; Cell Differentiation/physiology
مستخلص: Purpose: To investigate the roles of HDAC1/2 and HDAC3 in adult Meibomian gland (MG) homeostasis.
Methods: HDAC1/2 or HDAC3 were inducibly deleted in MG epithelial cells of adult mice. The morphology of MG was examined. Proliferation, apoptosis, and expression of MG acinus and duct marker genes, meibocyte differentiation genes, and HDAC target genes, were analyzed via immunofluorescence, TUNEL assay, and RNA in situ hybridization.
Results: Co-deletion of HDAC1/2 in MG epithelium caused gradual loss of acini and formation of cyst-like structures in the central duct. These phenotypes required homozygous deletion of both HDAC1 and HDAC2, indicating that they function redundantly in the adult MG. Short-term deletion of HDAC1/2 in MG epithelium had little effect on meibocyte maturation but caused decreased proliferation of acinar basal cells, excessive DNA damage, ectopic apoptosis, and increased p53 acetylation and p16 expression in the MG. By contrast, HDAC3 deletion in MG epithelium caused dilation of central duct, atrophy of acini, defective meibocyte maturation, increased acinar basal cell proliferation, and ectopic apoptosis and DNA damage. Levels of p53 acetylation and p21 expression were elevated in HDAC3-deficient MGs, while the expression of the differentiation regulator PPARγ and the differentiation markers PLIN2 and FASN was downregulated.
Conclusions: HDAC1 and HDAC2 function redundantly in adult Meibomian gland epithelial progenitor cells and are essential for their proliferation and survival, but not for acinar differentiation, while HDAC3 is required to limit acinar progenitor cell proliferation and permit differentiation. HDAC1/2 and HDAC3 have partially overlapping roles in maintaining survival of MG cells.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: P30 AR079200 United States AR NIAMS NIH HHS; R01 AR081322 United States AR NIAMS NIH HHS; R37 AR047709 United States AR NIAMS NIH HHS
فهرسة مساهمة: Keywords: Dry eye disease; HDAC1; HDAC2; HDAC3; Histone deacetylase; Meibomian gland homeostasis; p53
المشرفين على المادة: EC 3.5.1.98 (Histone Deacetylase 1)
EC 3.5.1.98 (Histone Deacetylases)
EC 3.5.1.98 (Histone Deacetylase 2)
EC 3.5.1.98 (histone deacetylase 3)
EC 3.5.1.98 (Hdac1 protein, mouse)
EC 3.5.1.98 (Hdac2 protein, mouse)
تواريخ الأحداث: Date Created: 20240428 Date Completed: 20240614 Latest Revision: 20240627
رمز التحديث: 20240627
مُعرف محوري في PubMed: PMC11179976
DOI: 10.1016/j.jtos.2024.04.005
PMID: 38679196
قاعدة البيانات: MEDLINE
الوصف
تدمد:1937-5913
DOI:10.1016/j.jtos.2024.04.005