Abstract
BackgroundCarbonic 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 Sentrix®Mouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR.ResultsCA 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.ConclusionsMicroarray 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.
Highlights
Carbonic anhydrases (CAs) are a family of enzymes that regulate pH homeostasis in various tissues
A previous study examined whether the effects of CA IX deficiency could be modified by a high-salt diet, a known co-factor of carcinogenesis [17]. These results showed that the high-salt diet slightly increased the glandular atrophy in the body mucosa in Car9-/- C57BL/6 mice, whereas this effect was not observed in BALB/c mice
This cut-off value has been proposed as an adequate level above which there is a high correlation between microarray and quantitative real-time PCR (QRT-PCR) data, regardless of other factors such as spot intensity and cycle threshold [18]
Summary
Carbonic anhydrases (CAs) are a family of enzymes that regulate pH homeostasis in various tissues. CA IX likely regulates cell proliferation and differentiation, which was demonstrated in Car9-/- mice. We wanted to study the effect of CA IX deficiency on whole-genome gene expression in gastric mucosa. The carbonic anhydrases (CAs) are a family of zinc-containing metalloenzymes that catalyze the reversible hydration of carbon dioxide in the reaction: CO2 + H2O H+ + HCO3-. They participate in several physiological processes, such as acid-base balance, CO2 and HCO3transport, respiration, bone resorption, ureagenesis, gluconeogenesis, lipogenesis, production of body fluids, and fertilization [1,2]. Using MDCK (Madin-Darby canine kidney) epithelial cells, it was shown that CA IX reduces E-cadherinmediated cell-cell adhesion by interacting with β-catenin [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
