BACKGROUND Sexual dimorphism in biological responses is a critical knowledge for therapeutic proposals. However, gender differences in intestinal stem cell physiology have been poorly studied. Given the important role of the protease-activated receptor PAR2 in the control of colon epithelial primitive cells and cell cycle genes, we have performed a sex-based comparison of its expression and of the effects of PAR2 activation or knockout on cell proliferation and survival functions. METHODS Epithelial primitive cells isolated from colons from male and female mice were cultured as colonoids, and their number and size were measured. PAR2 activation was triggered by the addition of SLIGRL agonist peptide in the culture medium. PAR2-deficient mice were used to study the impact of PAR2 expression on colon epithelial cell culture and gene expression. RESULTS Colonoids from female mice were more abundant and larger compared to males, and these differences were further increased after PAR2 activation by specific PAR2 agonist peptide. The proliferation of male epithelial cells was lower compared to females but was specifically increased in PAR2 knockout male cells. PAR2 expression was higher in male colon cells compared to females and controlled the gene expression and activation of key negative signals of the primitive cell proliferation. This PAR2-dependent brake on the proliferation of male colon primitive cells was correlated with stress resistance. CONCLUSIONS Altogether, these data demonstrate that there is a sexual dimorphism in the PAR2-dependent regulation of primitive cells of the colon crypt.

中文翻译：

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性二态性在原始结肠细胞的PAR2依赖性调节中。

背景技术生物学反应中的性二态性是治疗方案的关键知识。但是，对肠道干细胞生理学上的性别差异的研究很少。鉴于蛋白酶激活受体PAR2在控制结肠上皮原始细胞和细胞周期基因中的重要作用，我们已对其表达以及PAR2激活或敲除对细胞增殖和存活功能的影响进行了基于性别的比较。方法以雄性和雌性小鼠结肠分离的上皮原始细胞为类结肠，并对其数量和大小进行测定。通过在培养基中添加SLIGRL激动剂肽来触发PAR2激活。PAR2缺陷小鼠用于研究PAR2表达对结肠上皮细胞培养和基因表达的影响。结果与雄性小鼠相比，雌性小鼠的类结肠更丰富，更大，在特异性PAR2激动剂激活PAR2后，这些差异进一步增加。与雌性相比，雄性上皮细胞的增殖较低，但在PAR2敲除雄性细胞中则特异性增加。与雌性相比，雄性结肠细胞中的PAR2表达更高，并控制基因表达和原始细胞增殖关键负信号的激活。对雄性结肠原始细胞增殖的这种依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。这些差异在PAR2激活后被特异性PAR2激动剂肽进一步增加。与雌性相比，雄性上皮细胞的增殖较低，但在PAR2敲除雄性细胞中则特异性增加。与雌性相比，雄性结肠细胞中的PAR2表达更高，并控制基因表达和原始细胞增殖关键负信号的激活。对雄性结肠原始细胞增殖的这种依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。这些差异在PAR2激活后被特异性PAR2激动剂肽进一步增加。与雌性相比，雄性上皮细胞的增殖较低，但在PAR2敲除雄性细胞中则明显增加。与雌性相比，雄性结肠细胞中的PAR2表达更高，并控制基因表达和原始细胞增殖关键负信号的激活。这种对雄性结肠原始细胞增殖的依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。与雌性相比，雄性上皮细胞的增殖较低，但在PAR2敲除雄性细胞中则特异性增加。与雌性相比，雄性结肠细胞中的PAR2表达更高，并控制基因表达和原始细胞增殖关键负信号的激活。对雄性结肠原始细胞增殖的这种依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。与雌性相比，雄性上皮细胞的增殖较低，但在PAR2敲除雄性细胞中则特异性增加。与雌性相比，雄性结肠细胞中的PAR2表达更高，并控制基因表达和原始细胞增殖关键负信号的激活。对雄性结肠原始细胞增殖的这种依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。对雄性结肠原始细胞增殖的这种依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。对雄性结肠原始细胞增殖的这种依赖于PAR2的制动与抗逆性相关。结论总的来说，这些数据表明在结肠隐窝的原始细胞的PAR2依赖性调节中存在性二态性。