半乳糖凝集素-3缺失对人永生化角质形成细胞脂质代谢的影响

doi:10.3969/j.issn.1006-5725.2026.09.015

摘要/Abstract

摘要：

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。

关键词: 银屑病, 半乳糖凝集素-3, 脂质代谢, 过氧化物酶体增殖物激活受体-γ

Abstract:

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.

Key words: psoriasis, galectin-3, lipid metabolism, peroxisome proliferator-activated receptor-γ

中图分类号:

R751

蔡宇,黄锐,王德成,晁金,王雨馨,程美琦,韩珊珊. 半乳糖凝集素-3缺失对人永生化角质形成细胞脂质代谢的影响[J]. 实用医学杂志, 2026, 42(9): 1600-1609.

Yu CAI,Rui HUANG,Decheng WANG,Jin CHAO,Yuxin WANG,Meiqi CHENG,Shanshan HAN. Galectin-3 deficiency alters lipid metabolism in human immortalized keratinocytes[J]. The Journal of Practical Medicine, 2026, 42(9): 1600-1609.

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siRNA名称	上游引物序列（5’－3’）	下游引物序列（5’－3’）
Negative control	5’-UUCUCCGAACGUGUGACGUTT-3’	5’-ACGUGACACGUUCGGAGAATT-3’
LGALS3-homo-422	5’-GCCACUGAUUGUGCCUUAUTT-3’	5’-AUAAGGCACAAUCAGUGGCTT-3’
LGALS3-homo-746	5’-GUACAAUCAUCGGGUUAAATT-3’	5’-UUUAACCCGAUGAUUGUACTT-3’
LGALS3-homo-568	5’-CACGCUUCAAUGAGAACAATT-3’	5’-UUGUUCUCAUUGAAGCGUGTT-3’

基因	上游引物序列（5’－3’）	下游引物序列（5’－3’）
GAPDH	5’-GATCATCAGCAATGCCTCCTG-3’	5’-TGGGTGGCAGTGATGGCATG-3’
Gal3	5’-GCTGGGCCACTGATTGTGC-3’	5’-CTGTTTGCATTGGGCTTCAC-3’
PPAR-α	5’-GGCGAGGATAGTTCTGGAAGC-3’	5’-CACAGGATAAGTCACCGAGGAG-3’
PPAR-β	5’-GACATGACCTGGCCCTATTCA-3’	5’-AGGATGGTGTCCTGGATAGCCT-3’
PPAR-γ	5’-TAATGCCATCAGGTTGGGC-3’	5’-GGTCAGCGGACTCTGGATT-3’
IL-6	5’-TGAGAGTAGTGAGGAACAAG-3’	5’-CGCAGAATGAGATGAGTTG-3’
IL-17A	5’-GAGCTTCATCTGCTGACTAGAAC-3’	5’-GCCAAGGGAGTTAAAGACTTTG-3’
CXCL-1	5’-ACCGAAGTCATAGCCACAC-3’	5’-GTTGGATTTGTCACTGTTCAG-3’
TNF-α	5’-GCCCAGGCAGTCAGATCATC-3’	5’-CATTGGCCCGGCGGTTCAG-3’
S100A8	5’-GTATATCAGGAAAAAGGGTGCA-3’	5’-CTGCCACGCCCATCTTTAT-3’
E-FABP	5’-GCATTGGTTCAGCATCAG-3’	5’-TCCGAGTACAGGTGACAT-3’
FABP4	5’-GCATGGCCAAACCTAACA-3’	5’-GGCCCAGTATGAAGGAAATC-3’
BNIP3	5’-ACCACAAGATACCAACAGAG-3’	5’-CAATATCATCTTCCTCAGACTG-3’