Institute of Medical Technology and School of Medicine, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland.
BMC Genomics. 2010 Jun 23;11:397. doi: 10.1186/1471-2164-11-397.
Carbonic anhydrases (CAs) are a family of enzymes that regulate pH homeostasis in various tissues. CA IX is an exceptional member of this family because in addition to the basic CA function, it has been implicated in several other physiological and pathological processes. Functions suggested for CA IX include roles in cell adhesion and malignant cell invasion. In addition, CA IX likely regulates cell proliferation and differentiation, which was demonstrated in Car9-/- mice. These mice had gastric pit cell hyperplasia and depletion of chief cells; however, the specific molecular mechanisms behind the observed phenotypes remain unknown. Therefore, we wanted to study the effect of CA IX deficiency on whole-genome gene expression in gastric mucosa. This was done using Illumina SentrixMouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR.
CA IX deficiency caused the induction of 86 genes and repression of 46 genes in the gastric mucosa. There was 92.9% concordance between the results obtained by microarray analysis and QRT-PCR. The differentially expressed genes included those involved in developmental processes and cell differentiation. In addition, CA IX deficiency altered the expression of genes responsible for immune responses and downregulated the expression of several digestive enzymes.
Microarray analysis identified several potential genes whose altered expression could explain the disturbed cell lineage phenotype in the Car9-/- gastric mucosa. The results also indicated a novel role for CA IX in the regulation of immunologic processes and digestion. These findings reinforce the concept that the main role of CA IX is not the regulation of pH in the stomach mucosa. Instead, it is needed for proper function of several physiological processes.
碳酸酐酶（CA）是一组调节各种组织中 pH 平衡的酶。CAIX 是该家族的一个特殊成员，因为除了基本的 CA 功能外，它还与几种其他生理和病理过程有关。CAIX 的功能包括在细胞黏附和恶性细胞侵袭中起作用。此外，CAIX 可能调节细胞增殖和分化，这在 Car9-/-小鼠中得到了证明。这些小鼠的胃小凹细胞增生和主细胞耗竭；然而，观察到的表型背后的具体分子机制尚不清楚。因此，我们希望研究 CAIX 缺乏对胃黏膜全基因组基因表达的影响。这是通过使用 Illumina SentrixMouse-6 表达珠阵列来完成的。通过 QRT-PCR 确认了几个具有显著倍数变化值的基因的表达。
CAIX 缺乏导致胃黏膜中 86 个基因的诱导和 46 个基因的抑制。微阵列分析和 QRT-PCR 获得的结果有 92.9%的一致性。差异表达的基因包括参与发育过程和细胞分化的基因。此外，CAIX 缺乏改变了负责免疫反应的基因的表达，并下调了几种消化酶的表达。
微阵列分析确定了几个潜在的基因，其表达的改变可以解释 Car9-/-胃黏膜中紊乱的细胞谱系表型。结果还表明 CAIX 在调节免疫过程和消化中的新作用。这些发现强化了 CAIX 的主要作用不是调节胃黏膜中的 pH 的概念。相反，它是几个生理过程正常功能所必需的。
