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Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development.

Liao SY, Lerman MI, Stanbridge EJ - BMC Dev. Biol. (2009)

Bottom Line: Co-localization of CAXII with CAIX or HIF-1alpha was not observed.The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively.The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, St. Joseph Hospital, Orange, CA, USA. syliao@uci.edu

ABSTRACT

Background: Transmembrane CAIX and CAXII are members of the alpha carbonic anhydrase (CA) family. They play a crucial role in differentiation, proliferation, and pH regulation. Expression of CAIX and CAXII proteins in tumor tissues is primarily induced by hypoxia and this is particularly true for CAIX, which is regulated by the transcription factor, hypoxia inducible factor-1 (HIF-1). Their distributions in normal adult human tissues are restricted to highly specialized cells that are not always hypoxic. The human fetus exists in a relatively hypoxic environment. We examined expression of CAIX, CAXII and HIF-1alpha in the developing human fetus and postnatal tissues to determine whether expression of CAIX and CAXII is exclusively regulated by HIF-1.

Results: The co-localization of CAIX and HIF-1alpha was limited to certain cell types in embryonic and early fetal tissues. Those cells comprised the primitive mesenchyma or involved chondrogenesis and skin development. Transient CAIX expression was limited to immature tissues of mesodermal origin and the skin and ependymal cells. The only tissues that persistently expressed CAIX protein were coelomic epithelium (mesothelium) and its remnants, the epithelium of the stomach and biliary tree, glands and crypt cells of duodenum and small intestine, and the cells located at those sites previously identified as harboring adult stem cells in, for example, the skin and large intestine. In many instances co-localization of CAIX and HIF-1alpha was not evident. CAXII expression is restricted to cells involved in secretion and water absorption such as parietal cells of the stomach, acinar cells of the salivary glands and pancreas, epithelium of the large intestine, and renal tubules. Co-localization of CAXII with CAIX or HIF-1alpha was not observed.

Conclusion: The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively. The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

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Comparison of CAIX and CAXII expression during human development. There is no correlation between CAXII and CAIX expression. CAXII positive cells were distributed in taste buds and the submucosal gland of the tongue (A, 17W), the acinar cells of the pancreas (B, lower panel, but not ductal cells [B, upper panel]), the parietal cells but not columnar cells of the stomach (C1, 27W), the large intestine (D1, 17W), the distal tubules and collecting ducts of the kidney (E1, 8W), the choroid plexus (F1, 8W) and the remnants of mesonephric ducts of the ovary (G, 13W). In contrast, CAIX positive cells were seen in the gastric columnar cells (C2, 27W), the ependymal cells (F2, 8W), and the surface epithelial cells of the ovary and peritoneum (H, 13W). However, CAIX expression was not seen in the large intestine (D2, 17W), kidney (E2, 8W) and the remnants of the ovarian mesonephric ducts (H, 13W). W = gestational age in weeks. Original magnifications: A, F1 and F2 (20×); B, C1, C2, D1 and D2 (40×); E1, E2, G and H (10×).
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Figure 7: Comparison of CAIX and CAXII expression during human development. There is no correlation between CAXII and CAIX expression. CAXII positive cells were distributed in taste buds and the submucosal gland of the tongue (A, 17W), the acinar cells of the pancreas (B, lower panel, but not ductal cells [B, upper panel]), the parietal cells but not columnar cells of the stomach (C1, 27W), the large intestine (D1, 17W), the distal tubules and collecting ducts of the kidney (E1, 8W), the choroid plexus (F1, 8W) and the remnants of mesonephric ducts of the ovary (G, 13W). In contrast, CAIX positive cells were seen in the gastric columnar cells (C2, 27W), the ependymal cells (F2, 8W), and the surface epithelial cells of the ovary and peritoneum (H, 13W). However, CAIX expression was not seen in the large intestine (D2, 17W), kidney (E2, 8W) and the remnants of the ovarian mesonephric ducts (H, 13W). W = gestational age in weeks. Original magnifications: A, F1 and F2 (20×); B, C1, C2, D1 and D2 (40×); E1, E2, G and H (10×).

Mentions: In contrast to CAIX, the expression of CAXII was limited to very few organ systems. The numbers of cells stained and the intensity of positive staining were consistent throughout the embryonic and fetal periods and into the entire adult life. Its expression was observed predominantly in cells derived from the mesonephric duct or those cells whose differentiated function involves secretion and proton pumping. The coelomic cell origin, cell differentiation and degree of cellular hypoxia (the latter playing a significant role in regulation of CAIX expression), probably play no significant role in regulation of CAXII expression. CAXII expression was first observed in syncytiotrophoblasts during the embryonic period. Between 7–12 weeks of gestation, high levels of CAXII expression were already seen in those tissues involved in secretion or pH regulation. For example, the taste buds and underlying glands of the tongue (Fig. 7A), pancreatic acinar cells (Fig. 7B) and acinar cells of the minor/major salivary glands, the parietal cells of the stomach (Fig. 7C1), the epithelium of the large intestine (Fig. 7D1), renal tubules (Fig. 7E1), and choroid plexus (Fig. 7F1). CAXII expression was also observed in the remnants of mesonephric ducts of the testis and the ovary (Fig. 7G), and the epithelium of the inner ear (data not shown). Variable degrees of CAXII immunopositivity were also observed in the basal cells of the respiratory mucosa and the squamous mucosa lining the oral cavity, esophagus, cervix, vagina and the anus (data not shown). All of the tissues that expressed CAXII during fetal development retained their expression after birth and throughout adult life [7]. A representative comparison of expression of CAIX and CAXII proteins is shown in figs 7C–7H. It appears that the majority of organ systems show no co-expression of CAXII and CAIX.


Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development.

Liao SY, Lerman MI, Stanbridge EJ - BMC Dev. Biol. (2009)

Comparison of CAIX and CAXII expression during human development. There is no correlation between CAXII and CAIX expression. CAXII positive cells were distributed in taste buds and the submucosal gland of the tongue (A, 17W), the acinar cells of the pancreas (B, lower panel, but not ductal cells [B, upper panel]), the parietal cells but not columnar cells of the stomach (C1, 27W), the large intestine (D1, 17W), the distal tubules and collecting ducts of the kidney (E1, 8W), the choroid plexus (F1, 8W) and the remnants of mesonephric ducts of the ovary (G, 13W). In contrast, CAIX positive cells were seen in the gastric columnar cells (C2, 27W), the ependymal cells (F2, 8W), and the surface epithelial cells of the ovary and peritoneum (H, 13W). However, CAIX expression was not seen in the large intestine (D2, 17W), kidney (E2, 8W) and the remnants of the ovarian mesonephric ducts (H, 13W). W = gestational age in weeks. Original magnifications: A, F1 and F2 (20×); B, C1, C2, D1 and D2 (40×); E1, E2, G and H (10×).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 7: Comparison of CAIX and CAXII expression during human development. There is no correlation between CAXII and CAIX expression. CAXII positive cells were distributed in taste buds and the submucosal gland of the tongue (A, 17W), the acinar cells of the pancreas (B, lower panel, but not ductal cells [B, upper panel]), the parietal cells but not columnar cells of the stomach (C1, 27W), the large intestine (D1, 17W), the distal tubules and collecting ducts of the kidney (E1, 8W), the choroid plexus (F1, 8W) and the remnants of mesonephric ducts of the ovary (G, 13W). In contrast, CAIX positive cells were seen in the gastric columnar cells (C2, 27W), the ependymal cells (F2, 8W), and the surface epithelial cells of the ovary and peritoneum (H, 13W). However, CAIX expression was not seen in the large intestine (D2, 17W), kidney (E2, 8W) and the remnants of the ovarian mesonephric ducts (H, 13W). W = gestational age in weeks. Original magnifications: A, F1 and F2 (20×); B, C1, C2, D1 and D2 (40×); E1, E2, G and H (10×).
Mentions: In contrast to CAIX, the expression of CAXII was limited to very few organ systems. The numbers of cells stained and the intensity of positive staining were consistent throughout the embryonic and fetal periods and into the entire adult life. Its expression was observed predominantly in cells derived from the mesonephric duct or those cells whose differentiated function involves secretion and proton pumping. The coelomic cell origin, cell differentiation and degree of cellular hypoxia (the latter playing a significant role in regulation of CAIX expression), probably play no significant role in regulation of CAXII expression. CAXII expression was first observed in syncytiotrophoblasts during the embryonic period. Between 7–12 weeks of gestation, high levels of CAXII expression were already seen in those tissues involved in secretion or pH regulation. For example, the taste buds and underlying glands of the tongue (Fig. 7A), pancreatic acinar cells (Fig. 7B) and acinar cells of the minor/major salivary glands, the parietal cells of the stomach (Fig. 7C1), the epithelium of the large intestine (Fig. 7D1), renal tubules (Fig. 7E1), and choroid plexus (Fig. 7F1). CAXII expression was also observed in the remnants of mesonephric ducts of the testis and the ovary (Fig. 7G), and the epithelium of the inner ear (data not shown). Variable degrees of CAXII immunopositivity were also observed in the basal cells of the respiratory mucosa and the squamous mucosa lining the oral cavity, esophagus, cervix, vagina and the anus (data not shown). All of the tissues that expressed CAXII during fetal development retained their expression after birth and throughout adult life [7]. A representative comparison of expression of CAIX and CAXII proteins is shown in figs 7C–7H. It appears that the majority of organ systems show no co-expression of CAXII and CAIX.

Bottom Line: Co-localization of CAXII with CAIX or HIF-1alpha was not observed.The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively.The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, St. Joseph Hospital, Orange, CA, USA. syliao@uci.edu

ABSTRACT

Background: Transmembrane CAIX and CAXII are members of the alpha carbonic anhydrase (CA) family. They play a crucial role in differentiation, proliferation, and pH regulation. Expression of CAIX and CAXII proteins in tumor tissues is primarily induced by hypoxia and this is particularly true for CAIX, which is regulated by the transcription factor, hypoxia inducible factor-1 (HIF-1). Their distributions in normal adult human tissues are restricted to highly specialized cells that are not always hypoxic. The human fetus exists in a relatively hypoxic environment. We examined expression of CAIX, CAXII and HIF-1alpha in the developing human fetus and postnatal tissues to determine whether expression of CAIX and CAXII is exclusively regulated by HIF-1.

Results: The co-localization of CAIX and HIF-1alpha was limited to certain cell types in embryonic and early fetal tissues. Those cells comprised the primitive mesenchyma or involved chondrogenesis and skin development. Transient CAIX expression was limited to immature tissues of mesodermal origin and the skin and ependymal cells. The only tissues that persistently expressed CAIX protein were coelomic epithelium (mesothelium) and its remnants, the epithelium of the stomach and biliary tree, glands and crypt cells of duodenum and small intestine, and the cells located at those sites previously identified as harboring adult stem cells in, for example, the skin and large intestine. In many instances co-localization of CAIX and HIF-1alpha was not evident. CAXII expression is restricted to cells involved in secretion and water absorption such as parietal cells of the stomach, acinar cells of the salivary glands and pancreas, epithelium of the large intestine, and renal tubules. Co-localization of CAXII with CAIX or HIF-1alpha was not observed.

Conclusion: The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively. The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

Show MeSH
Related in: MedlinePlus