Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice.
Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice.
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DOI：
10.3748/wjg.v28.i47.6752
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发表时间：
2022-12-21
影响因子：
4.3
通讯作者：
Bian ZL
中科院分区：
文献类型：
--
作者：
Liu ZX;Chen WJ;Wang Y;Chen BQ;Liu YC;Cheng TC;Luo LL;Chen L;Ju LL;Liu Y;Li M;Feng N;Shao JG;Bian ZL
虽然白细胞介素（IL）-34在活动期溃疡性结肠炎（UC）中表达上调，但其分子功能和潜在机制尚不清楚。研究IL-34在急性结肠炎、伤口愈合模型和IL-34缺陷小鼠结肠炎相关癌症中的功能。结肠炎由葡聚糖硫酸钠（DSS）诱导，致癌作用由氧化偶氮甲烷（AOM）诱导。IL-34对结肠炎的影响是否依赖于巨噬细胞，通过小鼠模型中巨噬细胞的消耗来验证。在活动性UC患者中研究了IL-34表达与上皮增殖之间的关联。IL-34缺乏在急性结肠炎和伤口愈合期加重小鼠结肠炎。IL-34对实验性结肠炎的作用不依赖于巨噬细胞分化和极化。在施用AOM和DSS后，IL-34缺陷型小鼠比野生型小鼠发生更多的肿瘤。野生型和IL-34缺陷型小鼠之间的肿瘤细胞分化程度无显著差异。如前所述，在活动性UC患者中IL-34显著增加。更重要的是，UC患者中IL-34的表达与上皮细胞增殖正相关。IL-34缺乏会加重结肠炎症并加速小鼠结肠炎相关的致癌作用。它可能成为UC治疗的一个潜在靶点。
Although expression of interleukin (IL)-34 is upregulated in active ulcerative colitis (UC), the molecular function and underlying mechanism are largely unclear. To investigate the function of IL-34 in acute colitis, in a wound healing model and in colitis-associated cancer in IL-34-deficient mice. Colitis was induced by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by azoxymethane (AOM). Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model. The association between IL-34 expression and epithelial proliferation was studied in patients with active UC. IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase. The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization. IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS. No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice. IL-34 was dramatically increased in the active UC patients as previously reported. More importantly, expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC. IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice. It might be served as a potential therapeutic target in UC.
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影响因子：
10.6
作者：
Freuchet, Antoine;Salama, Apolline;Bezie, Severine;Tesson, Laurent;Remy, Severine;Humeau, Romain;Regue, Hadrien;Serazin, Celine;Flippe, Lea;Peterson, Part;Vimond, Nadege;Usal, Claire;Menoret, Severine;Heslan, Jean-Marie;Duteille, Franck;Blanchard, Frederic;Giral, Magali;Colonna, Marco;Anegon, Ignacio;Guillonneau, Carole
通讯作者：
Guillonneau, Carole
影响因子：
7.3
作者：
通讯作者：
--
影响因子：
--
作者：
Franzè E;Dinallo V;Rizzo A;Di Giovangiulio M;Bevivino G;Stolfi C;Caprioli F;Colantoni A;Ortenzi A;Grazia AD;Sica G;Sileri PP;Rossi P;Monteleone G
通讯作者：
Monteleone G
影响因子：
5.2
作者：
Franzè E;Di Grazia A;Sica GS;Biancone L;Laudisi F;Monteleone G
通讯作者：
Monteleone G
溃疡性结肠炎。
DOI：
10.1016/s0140-6736(16)32126-2
发表时间：
2017-04-29
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ungaro R;Mehandru S;Allen PB;Peyrin-Biroulet L;Colombel JF
通讯作者：
Colombel JF