Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea.
College of Pharmacy, Chungbuk National University, Chungju 28644, Republic of Korea.
Int J Mol Sci. 2024 Sep 2;25(17):9530. doi: 10.3390/ijms25179530.
Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (), olfactory receptor 870 (), pancreatic lipase (), and alkaline phosphatase intestinal (). Specifically, the gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that plays an important role as the novel gene associated with C3 deficiency-induced constipation.
补体成分 3 (C3) 缺乏症最近被报道为便秘的新原因之一。为了鉴定出由 C3 缺乏引起的便秘的独特基因，从 C3 基因敲除 (C3 KO) 小鼠的中结肠提取总 RNA 并与寡核苷酸微阵列杂交，并在体外和体内模型中验证候选基因的功能。用于微阵列的 C3 KO 小鼠表现出明确的便秘表型。总体而言，与野生型 (WT) 相比，C3 KO 小鼠中有 1237 个基因上调，1292 个基因下调。其中，主要的基因包括赖氨酸 (K)-特异性脱甲基酶 5D ()、嗅觉受体 870 ()、胰脂肪酶 () 和肠碱性磷酸酶 ()。具体而言，根据洛哌丁胺 (Lop) 诱导的便秘和炎症性肠病 (IBD) 期间的变化，选择 基因作为新的候选基因。用乙酸处理可上调 表达，可恢复 C3 KO 小鼠原代上皮细胞中粘蛋白相关基因的表达水平以及 C3 KO 小鼠的大多数便秘表型。这些结果表明 作为与 C3 缺乏引起的便秘相关的新型基因发挥着重要作用。
