Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach

Heini Kallio (Corresponding Author), Mika Hilvo, Alejandra Rodriguez, Eeva-Helena Lappalainen, Anna-Maria Lappalainen, Seppo Parkkila

Research output: Contribution to journalArticleScientificpeer-review

8 Citations (Scopus)

Abstract

Background - 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 Sentrix®Mouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR.

Results - 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.

Conclusions - 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.
Original languageEnglish
JournalBMC Genomics
Volume11
Issue number397
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Stomach
Gastric Mucosa
Physiological Phenomena
Carbonic Anhydrases
Microarray Analysis
Gene Expression
Genes
Cell Differentiation
Phenotype
Polymerase Chain Reaction
Carbonic Anhydrase IX
Cell Lineage
Pathologic Processes
Enzymes
Cell Adhesion
Hyperplasia
Digestion
Mucous Membrane
Homeostasis
Down-Regulation

Cite this

Kallio, H., Hilvo, M., Rodriguez, A., Lappalainen, E-H., Lappalainen, A-M., & Parkkila, S. (2010). Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach. BMC Genomics, 11(397). https://doi.org/10.1186/1471-2164-11-397
Kallio, Heini ; Hilvo, Mika ; Rodriguez, Alejandra ; Lappalainen, Eeva-Helena ; Lappalainen, Anna-Maria ; Parkkila, Seppo. / Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach. In: BMC Genomics. 2010 ; Vol. 11, No. 397.
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title = "Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach",
abstract = "Background - 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 Sentrix{\circledR}Mouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR.Results - 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.Conclusions - 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.",
author = "Heini Kallio and Mika Hilvo and Alejandra Rodriguez and Eeva-Helena Lappalainen and Anna-Maria Lappalainen and Seppo Parkkila",
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Kallio, H, Hilvo, M, Rodriguez, A, Lappalainen, E-H, Lappalainen, A-M & Parkkila, S 2010, 'Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach', BMC Genomics, vol. 11, no. 397. https://doi.org/10.1186/1471-2164-11-397

Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach. / Kallio, Heini (Corresponding Author); Hilvo, Mika; Rodriguez, Alejandra; Lappalainen, Eeva-Helena; Lappalainen, Anna-Maria; Parkkila, Seppo.

In: BMC Genomics, Vol. 11, No. 397, 2010.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach

AU - Kallio, Heini

AU - Hilvo, Mika

AU - Rodriguez, Alejandra

AU - Lappalainen, Eeva-Helena

AU - Lappalainen, Anna-Maria

AU - Parkkila, Seppo

PY - 2010

Y1 - 2010

N2 - Background - 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 Sentrix®Mouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR.Results - 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.Conclusions - 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.

AB - Background - 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 Sentrix®Mouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR.Results - 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.Conclusions - 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.

U2 - 10.1186/1471-2164-11-397

DO - 10.1186/1471-2164-11-397

M3 - Article

VL - 11

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 397

ER -

Kallio H, Hilvo M, Rodriguez A, Lappalainen E-H, Lappalainen A-M, Parkkila S. Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach. BMC Genomics. 2010;11(397). https://doi.org/10.1186/1471-2164-11-397