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

Abstract

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

CLC Number:

R751

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.

Figures/Tables 6

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References 34

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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’

Galectin-3 deficiency alters lipid metabolism in human immortalized keratinocytes

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