Lipolysis-stimulated lipoprotein receptor in intestinal epithelium attenu-ates dextran sodium sulfate-induced colitis in mice
10.3969/j.issn.1000-4718.2024.11.016
- VernacularTitle:肠上皮脂解刺激脂蛋白受体减轻葡聚糖硫酸钠诱导的小鼠结肠炎
- Author:
Ying LI
1
;
Ziqi WANG
;
Hao LIU
;
Yongfeng GONG
;
Yanan AN
Author Information
1. 滨州医学院生理学教研室,山东 烟台 264003
- Keywords:
lipolysis-stimulated lipoprotein receptor;
dextran sodium sulfate;
adeno-associated virus;
inflam-matory bowel disease
- From:
Chinese Journal of Pathophysiology
2024;40(11):2114-2123
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the expression of lipolysis-stimulated lipoprotein receptor(LSR)in dextran sodium sulfate(DSS)-induced colitis mice,and the effects of Lsr-specific knockout and overexpression in intestinal epithe-lium on intestinal inflammation in colitis mice.METHODS:C57BL/6J mice were administered 3%(w/v)DSS in drink-ing water for 6 days to induce colitis.Following the experiment,RNA-seq was employed to screen differentially expressed genes between the control group and experimental group.Changes in LSR expression were assessed using RT-qPCR,Western blot,and immunofluorescence staining.Intestinal epithelial Lsr-specific knockout mice were generated using the Cre-loxP system and subjected to DSS-induced colitis.Colitis severity was evaluated through changes in body weight,dis-ease activity index(DAI)score,colon length,and hematoxylin-eosin(HE)staining.Additionally,serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and IL-18 were measured via ELISA.Immunofluorescence staining was utilized to detect neutrophil and macrophage infiltration in colon tissues,while periodic acid-Schiff(PAS)staining was used to observe goblet cell numbers.Furthermore,adeno-associated virus(AAV-Lsr)was intraperitoneally injected to achieve LSR overexpression.Successful LSR overexpression was confirmed,and a DSS-induced colitis model was established using similar methods to observe intestinal inflammation.RESULTS:Results showed decreased LSR ex-pression in DSS-induced colitis mice.Intestinal epithelial Lsr-specific knockout mice exhibited increased susceptibility to DSS-induced colitis,evidenced by significantly reduced body weight(P<0.05),increased DAI(P<0.01),shortened co-lon length(P<0.05),and exacerbated pathological injury.Levels of pro-inflammatory cytokines TNF-α(P<0.05),IL-1β(P<0.01),IL-6(P<0.05),and IL-18(P<0.01)were significantly elevated,along with increased inflammatory cell infiltration and reduced goblet cell numbers in the colon.Conversely,LSR overexpression via AAV significantly alleviated intestinal inflammation in DSS-induced colitis mice.CONCLUSION:In conclusion,LSR expression decreased in DSS-induced colitis mice,and its loss exacerbated intestinal inflammation in this model.AAV-mediated LSR overexpression provided therapeutic relief from intestinal inflammation in DSS-induced colitis mice.
