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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年03期

页码:

260-265

栏目:

基础医学

出版日期:

2022-05-20

文章信息/Info

Title:

CD24 inhibits the liver fibrosis process by regulating the secretion of PDGF -B in hepatic Ly6Clo macrophage subset

文章编号:

1006-8147(2022)03-0260-06

作者:

靳悦; 汪河; 李明威; 张学军

（天津医科大学基础医学院免疫学系，天津300070）

Author(s):

JIN Yue; WANG He; LI Ming-wei; ZHANG Xue-jun

（Department of Immunology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China）

关键词:

CD24 分子; 肝纤维化; 肝内Ly6Clo巨噬细胞; 肝星状细胞; PDGF-B

Keywords:

CD24 molecules; liver fibrosis; hepatic Ly6Clo macrophages; hepatic stellate cells; PDGF-B

分类号:

R392.1

DOI:

-

文献标志码:

A

摘要:

目的：探讨CD24 分子在胆总管结扎（BDL）诱导的小鼠胆汁淤积型肝纤维化中对肝内Ly6Clo巨噬细胞亚群的调节以及 分泌PDGF-B的影响。方法：建立小鼠胆总管结扎诱导的肝纤维化模型，将野生型（WT）与CD24 基因敲除（CD24-/-）雌性小鼠随 机分为造模组（BDL）与假手术组（Sham），每组5只，造模组进行胆总管结扎，假手术组与造模组手术处理相同但不结扎胆总管。 术后7 d 应用HE 和天狼星红（Sirius Red）染色分析小鼠肝组织病理变化和肝纤维化程度，定量-PCR（Q-PCR）和Western 印迹 检测肝内α-SMA 等纤维化因子的表达，流式细胞术分析CD24 分子在肝内巨噬细胞亚群中的表达，共培养实验检测肝内星状 细胞中纤维化因子的变化。结果：两种基因背景小鼠的假手术组无病理表现，在造模组中，CD24-/-小鼠与WT 小鼠相比肝纤维化 明显加重，表现为肝汇管区炎性细胞浸润增多，α-SMA 等肝纤维化标志物的表达升高。流式分析结果显示，CD24 分子在肝内 Ly6Clo 巨噬细胞亚群上高表达，在造模组中，CD24-/-鼠造模后肝内Ly6Clo 巨噬细胞亚群比例[（65.05±0.250）%]高于WT 鼠 [（52.55±2.950）]%，差异有统计学意义（P<0.05）。进一步研究发现：PDGF-B 在肝内Ly6Clo巨噬细胞亚群高表达，并且在CD24-/- 小鼠中的表达明显高于WT小鼠，差异有统计学意义（P<0.000 1）。结论：CD24分子可通过调节肝内Ly6Clo巨噬细胞亚群中PDGFB 分泌减缓肝纤维化进程。

Abstract:

Objective：To investigate the effect of CD24 on Ly6Clo macrophage subsets and secretion of PDGF-B in cholestatic liver fibrosis induced by common bile duct ligation（BDL）. Methods: A mouse model of BDL-induced liver fibrosis was established.Wild type （WT）and CD24 gene knockout（CD24-/-）female mice were randomly divided into model（BDL）group and sham group，with 5 mice in each group. The model group was subjected to common bile duct ligation. The sham group was the samesurgical treatment as that of model group，but the common bile duct was not ligated. Seven days after operation，the pathological changes of liver tissue and the degree of liver fibrosis were analyzed by HE and Sirius red staining. The expression of fibrosis factors such as α-SMA were detected by Western blotting and Q-PCR. The expression of CD24 in hepatic macrophages subsets was detected by flow cytometry. Co-culture assay was used to detect the changes of fibrotic factors in hepatic stellate cells. Results: There were no pathological manifestations in the sham operation group of mice with two genetic backgrounds.In the model group，the hepatic fibrosis of CD24-/- mice was significantly worse than that of WT mice，CD24-/- mice had more inflammatory cell infiltration in hepatic portal area，elevated α-SMA and other markers of hepatic fibrosis expression. Flow cytometry analysis showed that CD24 was highly expressed in Ly6Clo macrophage subsets in liver.The proportion of Ly6Clo macrophage subsets of CD24-/- mice[（65.05±0.250）%] was higher than WT mice[（52.55±2.950）%]，and the difference was statistically significant （P<0.05）. Further study found that PDGF-B was highly expressed in Ly6Clo macrophage subsets in liver，and the expression in CD24-/- mice was significantly higher than WT mice（P<0.000 1）.Conclusion: CD24 may alleviate the process of liver fibrosis by regulating the secretion of PDGF-B in hepatic Ly6Clo macrophage subset.

参考文献/References:

[1] KISSELEVA T，BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol， 2021，18（3）：151-166.
[2] TACKE F. Targeting hepatic macrophages to treat liver diseases[J]. J Hepatol，2017，66（6）：1300-1312.
[3] CAMPANA L，IREDALE J P. Regression of liver fibrosis [J]. Semin Liver Dis，2017，37（1）：1-10.
[4] TACKE F，ZIMMERMANN H W. Macrophage heterogeneity in liver injury and fibrosis[J]. J Hepatol，2014，60（5）：1090-1096.
[5] WOLLIN L，WEX E，PAUTSCH A，et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis[J]. Eur Respir J， 2015，45（5）：1434-1445.
[6] KOCABAYOGLU P，LADE A，LEE Y A，et al. β-PDGF receptor expressed by hepatic stellate cells regulates fibrosis in murine liver injury， but not carcinogenesis[J]. J Hepatol，2015，63（1）：141-147.
[7] GAO J，WEI B，DE ASSUNCAO T M，et al. Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis[ J]. J Hepatol，2020，73（5）：1144-1154.
[8] BARTNECK M，WARZECHA K T，TACKE F，et al. Therapeutic targeting of liver inflammation and fibrosis by nanomedicine [J]. Hepatobiliary Surg Nutr，2014，3（6）：364-376.
[9] YING H Z，CHEN Q，ZHANG W Y，et al. PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics（Review）[J]. Mol Med Rep，2017，16（6）：7879-7889.
[10] CAO S，YAQOOB U，DAS A，et al. Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancingPDGF/TGF-beta signaling in hepatic stellate cells[J]. J Clin Invest，2010，120 （7）：2379- 2394.
[11] CHEN G Y，BROWN N K，ZHENG P，et al. Siglec-G/10 in selfnonself discrimination of innate and adaptive immunity[J]. Glycobiology， 2014，24（9）：800-806.
[12] ALTEVOGT P，SAMMAR M，H譈SER L，et al. Novel insights into the function of CD24：a driving force in cancer[J]. Int J Cancer，2021， 148（3）：546-559.
[13] BARKAL A A，BREWER R E，MARKOVIC M，et al. CD24 signalling through macrophage Siglec -10 is a target for cancer immunotherapy[ J]. Nature，2019，572（7769）：392-396.
[14] BAI X F，LI Q，ZHOU Q，et al. CD24 controls expansion and persistence of autoreactive T cells in the central nervous system during experimental autoimmune encephalomyelitis[J]. J Exp Med，2004，200 （4）：447-458.
[15] HABIB A，CHOKR D，WAN J，et al. Inhibition of monoacylglycerol lipase，an anti -inflammatory and antifibrogenic strategy in the liver[J]. Gut，2019，68（3）：522-532.
[16] SUNY Y，LI X F，MENG X M，et al. Macrophage phenotype in liver injury and repair[J]. Scand J Immunol，2017，85（3）：166-174.
[17] WEN Y，LAMBRECHT J，JU C，et al. Hepatic macrophages in liver homeostasis and diseases-diversity，plasticity and therapeutic opportunities[ J]. Cell Mol Immunol，2021，18（1）：45-56.
[18] LI X，SHAO S，LI H，et al. Byakangelicin protects against carbon tetrachloride- induced liver injury and fibrosis in mice[J]. J Cell Mol Med，2020，24（15）：8623-8635.
[19] DISTLER JHW，GY魻RFI A H，RAMANUJAM M，et al. Shared and distinct mechanisms of fibrosis[J]. Nat Rev Rheumatol，2019，15（12）： 705-730.
[20] GU魪RIT E，ARTS F，DACHY G，et al. PDGF receptor mutations in human diseases[J]. Cell Mol Life Sci，2021，78（8）：3867-3881.

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备注/Memo

备注/Memo:

基金项目国家自然科学基金面上项目(31370891）；天津市自然科 学基金重点项目(18JCZDJC98300)
作者简介:靳悦（1996-），女，硕士在读，研究方向：巨噬细胞与肝纤 维化；
通信作者:张学军，E-mail:xjzh@tmu.edu.cn。

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更新日期/Last Update: 2022-06-01