Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Exp Dermatol. 2018 Nov;27(11):1254-1260. doi: 10.1111/exd.13775. Epub 2018 Sep 26.
Forkhead box-O1 (FoxO1) is a key nutrient- and growth factor-dependent regulator of metabolism, but its functional role in human primary keratinocytes (HPKs) is less known. To investigate the role of FoxO1 in HPKs and effect of insulin-like growth factor 1 (IGF-1) and isotretinoin on FoxO1 expression, HPKs were treated with 1.2 mmol/L calcium chloride, 1-20 ng/mL IGF-1 and 0.1-10 μmol/L isotretinoin. Recombinant adenovirus expressing FoxO1 or FKHR shRNA lentivirus transfection was introduced to upregulate or silence FoxO1 expression. Epidermal FoxO1 immunostaining was lower in acne lesion than in normal skin. FoxO1 overexpression induced involucrin expression, G2/M arrest and apoptosis but suppressed proliferation, while FoxO1 silencing decreased involucrin expression but increased proliferation, S phase and viable cells in HPKs. IGF-1 downregulated FoxO1 and involucrin but upregulated p-Akt expression in HPKs, which was blocked by pretreatment with LY294002. Isotretinoin enhanced FoxO1, p53 and p21 but inhibited p-FoxO1 and involucrin expression in HPKs. These results demonstrate that FoxO1 promotes differentiation and apoptosis in HPKs. IGF-1 may reduce keratinocyte differentiation through PI3K/Akt/FoxO1 pathway, while isotretinoin can reinforce FoxO1 expression. FoxO1 may be involved in acne pathogenesis and could serve as a potential therapeutic target.
叉头框蛋白 O1（FoxO1）是一种关键的营养和生长因子依赖性代谢调节因子，但它在人类原代角质形成细胞（HPKs）中的功能作用知之甚少。为了研究 FoxO1 在 HPKs 中的作用以及胰岛素样生长因子 1（IGF-1）和异维 A 酸对 FoxO1 表达的影响，用 1.2mmol/L 氯化钙、1-20ng/mL IGF-1 和 0.1-10μmol/L 异维 A 酸处理 HPKs。用表达 FoxO1 的重组腺病毒或 FKHR shRNA 慢病毒转染来上调或沉默 FoxO1 表达。痤疮皮损中的表皮 FoxO1 免疫染色比正常皮肤低。FoxO1 过表达诱导角蛋白 10 表达、G2/M 期阻滞和凋亡，但抑制增殖，而 FoxO1 沉默减少角蛋白 10 表达但增加增殖、S 期和 HPKs 中的存活细胞。IGF-1 下调 HPKs 中的 FoxO1 和角蛋白 10，但上调 p-Akt 表达，LY294002 预处理可阻断此作用。异维 A 酸增强 HPKs 中的 FoxO1、p53 和 p21，但抑制 p-FoxO1 和角蛋白 10 表达。这些结果表明 FoxO1 促进 HPKs 的分化和凋亡。IGF-1 可能通过 PI3K/Akt/FoxO1 通路减少角质形成细胞分化，而异维 A 酸可增强 FoxO1 表达。FoxO1 可能参与痤疮发病机制，可作为潜在的治疗靶点。
