Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
Department of Biosciences and Nutrition, Karolinska Institutet, 14186 Huddinge, Sweden.
Int J Mol Sci. 2023 Aug 5;24(15):12461. doi: 10.3390/ijms241512461.
Liver X receptors (LXRα and LXRβ) are oxysterol-activated nuclear receptors that play key roles in cholesterol homeostasis, the central nervous system, and the immune system. We have previously reported that LXRαβ-deficient mice are more susceptible to dextran sodium sulfate (DSS)-induced colitis than their WT littermates, and that an LXR agonist protects against colitis in mice mainly via the regulation of the immune system in the gut. We now report that both LXRα and LXRβ are expressed in the colonic epithelium and that in aging LXRαβ mice there is a reduction in the intensity of goblet cells, mucin (MUC2), TFF3, and estrogen receptor β (ERβ) levels. The cytoplasmic compartment of the surface epithelial cells was markedly reduced and there was a massive invasion of macrophages in the lamina propria. The expression and localization of β-catenin, α-catenin, and E-cadherin were not changed, but the shrinkage of the cytoplasm led to an appearance of an increase in staining. In the colonic epithelium there was a reduction in the expression of plectin, a hemidesmosome protein whose loss in mice leads to spontaneous colitis, ELOVL1, a fatty acid elongase protein coding gene whose overexpression is found in colorectal cancer, and non-neuronal choline acetyltransferase (ChAT) involved in the regulation of epithelial cell adhesion. We conclude that in aging LXRαβ mice, the phenotype in the colon is due to loss of ERβ expression.
肝 X 受体（LXRα 和 LXRβ）是氧化固醇激活的核受体，在胆固醇稳态、中枢神经系统和免疫系统中发挥关键作用。我们之前曾报道过，LXRαβ 缺陷小鼠比其 WT 同窝仔更容易发生葡聚糖硫酸钠（DSS）诱导的结肠炎，而 LXR 激动剂通过调节肠道中的免疫系统来预防结肠炎。我们现在报告 LXRα 和 LXRβ 都在结肠上皮细胞中表达，并且在衰老的 LXRαβ 小鼠中，杯状细胞、粘蛋白（MUC2）、TFF3 和雌激素受体β（ERβ）的强度降低。表面上皮细胞的细胞质区室明显减少，固有层中有大量巨噬细胞浸润。β-连环蛋白、α-连环蛋白和 E-钙粘蛋白的表达和定位没有改变，但细胞质的收缩导致染色增加。在结肠上皮细胞中，桥粒蛋白 plectin、脂肪酸延长酶蛋白编码基因 ELOVL1 和非神经元胆碱乙酰转移酶（ChAT）的表达减少，桥粒蛋白 plectin 的缺失会导致自发性结肠炎，ELOVL1 在结直肠癌中过度表达，非神经元胆碱乙酰转移酶（ChAT）参与上皮细胞黏附的调节。我们得出结论，在衰老的 LXRαβ 小鼠中，结肠的表型是由于 ERβ 表达的丧失。
