期刊
GLYCOBIOLOGY
卷 32, 期 1, 页码 73-82出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwab100
关键词
androgen; galectin-12; PPAR gamma; sebaceous glands
In this study, Galectin-12 was identified as an important intracellular regulator of sebocyte proliferation. It modulates cell cycle regulators and PPAR gamma expression to affect the proliferation of sebocytes. These findings suggest the potential of targeting Galectin-12 for the treatment of skin diseases related to sebaceous gland hyperfunction and androgens.
Enhanced sebocyte proliferation is associated with the pathogenesis of human skin diseases related to sebaceous gland hyperfunction and androgens, which are known to induce sebocyte proliferation, are key mediators of this process. Galectin-12, a member of the beta-galactoside-binding lectin family that is preferentially expressed by adipocytes and functions as an intrinsic negative regulator of lipolysis, has been shown to be expressed by human sebocytes. In this study, we identified galectin-12 as an important intracellular regulator of sebocyte proliferation. Galectin-12 knockdown in the human SZ95 sebocyte line suppressed cell proliferation, and its overexpression promoted cell cycle progression. Inhibition of galectin-12 expression reduced the androgen-induced SZ95 sebocyte proliferation and growth of sebaceous glands in mice, respectively. The mRNA expression of the key cell cycle regulators cyclin A1 (CCNA1) and cyclin-dependent kinase 2CDK2 was reduced in galectin-12 knockdown SZ95 sebocytes, suggesting a pathway of galectin-12 regulation of sebocyte proliferation. Further, galectin-12 enhanced peroxisome proliferator-activated receptor gamma (PPAR gamma) expression and transcriptional activity in SZ95 sebocytes, consistent with our previous studies in adipocytes. Rosiglitazone, a PPAR gamma ligand, induced CCNA1 levels, suggesting that galectin-12 may upregulate CCNA1 expression via PPAR gamma. Our findings suggest the possibility of targeting galectin-12 to treat human sebaceous gland hyperfunction and androgen-associated skin diseases.
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