To investigate the roles of HDAC1/2 and HDAC3 in adult Meibomian gland (MG) homeostasis. 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. 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 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. 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.

中文翻译：

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HDAC1/2 和 HDAC3 在控制成人睑板腺稳态中发挥不同作用


研究 HDAC1/2 和 HDAC3 在成人睑板腺 (MG) 稳态中的作用。成年小鼠的 MG 上皮细胞中 HDAC1/2 或 HDAC3 被诱导缺失。检查 MG 的形态。通过免疫荧光、TUNEL 测定和 RNA 原位杂交分析 MG 腺泡和导管标记基因、睑红细胞分化基因和 HDAC 靶基因的增殖、凋亡和表达。 MG 上皮中 HDAC1/2 的共同缺失导致腺泡逐渐丧失并在中央导管中形成囊肿样结构。这些表型需要 HDAC1 和 HDAC2 的纯合删除，表明它们在成人 MG 中功能冗余。 MG上皮中HDAC1/2的短期缺失对睑母细胞成熟影响不大，但会导致腺泡基底细胞增殖减少、DNA过度损伤、异位凋亡以及MG中p53乙酰化和表达增加。相比之下，MG上皮中HDAC3缺失导致中央导管扩张、腺泡萎缩、睑母细胞成熟缺陷、腺泡基底细胞增殖增加、异位凋亡和DNA损伤。在 HDAC3 缺陷的 MG 中，p53 乙酰化和 p21 表达水平升高，而分化调节因子 PPARγ 以及分化标记物 PLIN2 和 FASN 的表达下调。 HDAC1 和 HDAC2 在成年睑板腺上皮祖细胞中发挥冗余功能，对于其增殖和生存至关重要，但对于腺泡分化则不然，而 HDAC3 则需要限制腺泡祖细胞增殖并允许分化。 HDAC1/2 和 HDAC3 在维持 MG 细胞存活方面具有部分重叠的作用。