目的 探究半乳糖凝集素-3（galectin-3， Gal3）缺失对人永生化角质形成细胞脂质代谢的影响。 方法 通过体内外实验结合，体内实验利用咪喹莫特诱导法在Gal3野生型（Gal3^+/+ ）与Gal3全身基因敲除型（Gal3^-/- ）小鼠中构建银屑病小鼠模型，系统观察银屑病小鼠皮损组织的超微病理学结构和脂质堆积情况；体外实验在人永生化角质形成细胞（HaCaT细胞）内进行干扰与过表达实验，通过Western blot、RT-qPCR、EdU细胞增殖实验、油红O染色以及免疫荧光染色实验分析Gal3在银屑病相关炎症反应与脂质代谢中的作用。 结果 Gal3^-/- 银屑病小鼠皮损处脂滴明显富集，脂质聚集显著高于Gal3^+/+ 小鼠。细胞实验表明，下调Gal3表达可引起炎症因子IL-17A、TNF-α、S100A8表达显著升高（P < 0.001）、处于增殖期的细胞数量显著增多（P < 0.05）、细胞内脂质沉积增多，同时脂质代谢相关基因PPAR-γ（P < 0.05）、FABP4、E-FABP表达下调（P < 0.01）；过表达Gal3可逆转上述脂质代谢因子的表达（P < 0.05）。PPAR-γ激动剂罗格列酮（RGZ）可缓解Gal3低表达引起的脂质堆积，但Gal3不影响PPAR-γ的核定位，二者在胞质中无共定位。 结论 Gal3缺失可通过间接调控PPAR-γ信号通路，引发角质形成细胞脂质代谢异常并加剧银屑病相关脂质代谢紊乱。

Objective To investigate the impact of galectin-3 （Gal-3） deficiency on lipid metabolism in human immortalized keratinocytes and its role in psoriasis-associated pathology. Methods A combined in vivo and in vitro approach was employed. For the in vivo study， a psoriasis-like dermatitis model was induced by imiquimod （IMQ） in both Gal-3 wild-type （Gal3^+/+） and whole-body Gal-3 knockout （Gal3^-/-） mice. Skin lesions were systematically examined for ultrastructural pathological changes and lipid accumulation. For the in vitro study， Gal-3 knockdown and overexpression were performed in human immortalized keratinocytes （HaCaT cells）. The effects of Gal-3 modulation on psoriasis-related inflammation and lipid metabolism were evaluated using Western blotting， RT-qPCR， EdU proliferation assays， Oil Red O staining， and immunofluorescence. Results Lipid droplets were markedly enriched in the skin lesions of Gal3^-/- mice， showing significantly greater accumulation compared to Gal3^+/+ controls. In HaCaT cells， Gal-3 knockdown significantly upregulated the expression of inflammatory factors IL-17A， TNF-α， and S100A8 （P < 0.001）， increased the proportion of proliferating cells （P < 0.05）， promoted intracellular lipid deposition， and downregulated key lipid metabolism-related genes， including PPARγ （P < 0.05）， FABP4， and E-FABP （P < 0.01）. Conversely， Gal-3 overexpression reversed these alterations in lipid metabolic markers （P < 0.05）. Furthermore， treatment with the PPARγ agonist rosiglitazone （RGZ） alleviated the lipid accumulation induced by Gal-3 deficiency. Mechanistically， Gal-3 deficiency did not affect the nuclear localization of PPARγ， nor was any cytoplasmic co-localization between the two proteins observed. Conclusion Gal-3 deficiency exacerbates psoriasis-associated lipid metabolic disturbances by indirectly regulating the PPARγ signaling pathway， leading to aberrant lipid metabolism in keratinocytes. These findings suggest that Gal-3 plays a protective role in maintaining lipid homeostasis during psoriatic inflammation.