Home General Physiology and Biophysics 2026 General Physiology and Biophysics Vol.45, No.1, p, 107–120, 2026

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Founded: 1982
ISSN 1338-4325 (online)
ISSN 0231-5882 (print)
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General Physiology and Biophysics Vol.45, No.1, p, 107–120, 2026

Title: lincRNA-p21 inhibits foam cell formation and regulates cholesterol uptake and efflux in macrophages through the PKCδ/Akt/Erk and PPARγ/LXRα pathways
Author: Chao He, Wei Yang, Fei Zhou, Lin Teng, Hui Wu, Zhuli Guo, Jiawang Ding, Jing Zhang, Jian Yang, Song Li
Abstract:  Impairment in cholesterol uptake and efflux is the main reason contributing to foam cell formation, which is a marker and key step in the atherosclerotic process. Overexpression of long intergenic non-coding RNA-p21 (lincRNA-p21) was reported to alleviate the development of atherosclerosis. However, whether lincRNA-p21 exerts an antiatherogenic function by alleviating lipid metabolism dysfunction and foam cell formation remains unknown. In our study, human THP-1 monocytes were stimulated for 48 h by phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and THP-1-derived macrophages were further treated for 24 h with oxidized low-density lipoprotein (ox-LDL) to differentiate into foam cells. THP‑1 macrophage-derived foam cells were transfected with si-NC/si-lincRNA-p21 or LV-NC/LV-lincRNA-p21 for 48 h to knock down or overexpress lincRNA-p21. lincRNA-p21 expression was reduced in THP-1-derived macrophages after ox-LDL treatment. lincRNA-p21 knockdown promoted lipid uptake and accumulation and inhibited cholesterol efflux in ox-LDL-treated THP-1 macrophages, while lincRNA-p21 overexpression exerted an opposite effect on cholesterol influx and efflux. Importantly, lincRNA-p21 attenuated cholesterol influx by suppressing the PKCδ/Akt/Erk/SR-A/CD36 pathway and enhanced cholesterol efflux by promoting the PPARγ/LXRα/ABCA1/ABCG1 pathway in foam cells derived from THP-1 macrophages.
Keywords: lincRNA‐p21 — Atherosclerosis — Lipid uptake — Cholesterol efflux — PKCδ — PPARγ
Year: 2026, Volume: 45, Issue: 1 Page From: 107, Page To: 120
doi:10.4149/gpb_2025040
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