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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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The correlation between CAIX and HIF-1α expression during human development. In the early stage (5–9 weeks of gestation) diffuse HIF-1α immunoreactivity was seen in the CNS (A), primitive intestine (B), chorionic villi (C) and chondrocytes of the disc (D), mesenchymal cells and chondrocytes of the limb (E), and the skin (E arrow). In contrast, no CAIX expression was seen in the CNS (A), primitive intestine (B), and chorionic villi (C). Co-expression of HIF-1α and CAIX was seen in the skin (E) and the cells involved in chondrogenesis (D, E). During later human development, around 19–20 weeks, HIF-1α expression was persistently observed in the kidney (F) and rectum (G) but no CAIX expressing cells were seen in these organs. However, a degree of overlap between CAIX and HIF-1α expression was seen in the skin (H), squamous mucosa of the vagina and the cervix (I and J). W = gestational age in weeks. Original magnifications: A, B, D-H (40×); C (left panel 20×; right panel 40×); I (20×); J (left panel 20×; right panel 40×).
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Figure 8: The correlation between CAIX and HIF-1α expression during human development. In the early stage (5–9 weeks of gestation) diffuse HIF-1α immunoreactivity was seen in the CNS (A), primitive intestine (B), chorionic villi (C) and chondrocytes of the disc (D), mesenchymal cells and chondrocytes of the limb (E), and the skin (E arrow). In contrast, no CAIX expression was seen in the CNS (A), primitive intestine (B), and chorionic villi (C). Co-expression of HIF-1α and CAIX was seen in the skin (E) and the cells involved in chondrogenesis (D, E). During later human development, around 19–20 weeks, HIF-1α expression was persistently observed in the kidney (F) and rectum (G) but no CAIX expressing cells were seen in these organs. However, a degree of overlap between CAIX and HIF-1α expression was seen in the skin (H), squamous mucosa of the vagina and the cervix (I and J). W = gestational age in weeks. Original magnifications: A, B, D-H (40×); C (left panel 20×; right panel 40×); I (20×); J (left panel 20×; right panel 40×).

Mentions: Recent evidence indicates that the fetus exists in a relatively hypoxic environment. The fetal PO2 is 35 mm of Hg compared with 100 mm of Hg in the adult [23]. HIF-1α mRNA is constitutively expressed in all organs and at all stages of gestation from 14–22 weeks, with the highest expression noted in the brain, heart, kidney, lung and liver [23]. However, HIF-1α protein is rapidly degraded in the proteasome, via VHL E3 ligase recognition, under normoxic conditions and is stabilized under hypoxic conditions [2,3]. In the transgenic mouse model study conducted by Provot et al., they found that HIF-1α protein is stably expressed and transcriptionally active in limb bud mesenchyme and in mesenchyme condensations during fetal development [24]. Thus, HIF-1 appears to play an important role in early chondrogenesis and joint formation. We performed an immunohistochemical study for HIF-1α expression on the fetal tissues, representing all stages of human development from 5–38 weeks of gestation, and encompassing both embryonic and fetal development. We found that as early as 5–9 weeks of gestation, diffuse HIF-1α nuclear immunoreactivity was seen in most of the embryonic and fetal tissues, particularly in the endothelial cells, body mesenchymal cells and nervous system (Fig. 8A), primitive gastrointestinal tract (Fig. 8B), and the chondrocytes and mesenchyme of vertebral disc/limb bud (Fig. 8D, 8E). In the skin, HIF-1α expression was consistently observed during fetal development (Fig. 8E, 8H). Interestingly, the immature chorionic villi during the 1st trimester also showed diffuse HIF-1α nuclear staining (Fig. 8C) and this observation is consistent with that previously published [26]. Variable degrees of HIF-1α expression were also observed in the visceral organs, especially during 17–25 weeks of gestation. The best examples are shown in fig 8F (kidney) and 8G (rectum). Although HIF-1α expression was persistent throughout the fetal period, the numbers of expressing cells progressively diminished. During the last trimester of fetal development (27–40 weeks) stable HIF-1α expression was limited to chondrocytes, endothelial cells, skin, and epithelial cells of the squamous mucosa, such as the vagina and cervix (Fig. 8I, 8J), the oral cavity, esophagus and anus.


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

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

The correlation between CAIX and HIF-1α expression during human development. In the early stage (5–9 weeks of gestation) diffuse HIF-1α immunoreactivity was seen in the CNS (A), primitive intestine (B), chorionic villi (C) and chondrocytes of the disc (D), mesenchymal cells and chondrocytes of the limb (E), and the skin (E arrow). In contrast, no CAIX expression was seen in the CNS (A), primitive intestine (B), and chorionic villi (C). Co-expression of HIF-1α and CAIX was seen in the skin (E) and the cells involved in chondrogenesis (D, E). During later human development, around 19–20 weeks, HIF-1α expression was persistently observed in the kidney (F) and rectum (G) but no CAIX expressing cells were seen in these organs. However, a degree of overlap between CAIX and HIF-1α expression was seen in the skin (H), squamous mucosa of the vagina and the cervix (I and J). W = gestational age in weeks. Original magnifications: A, B, D-H (40×); C (left panel 20×; right panel 40×); I (20×); J (left panel 20×; right panel 40×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666674&req=5

Figure 8: The correlation between CAIX and HIF-1α expression during human development. In the early stage (5–9 weeks of gestation) diffuse HIF-1α immunoreactivity was seen in the CNS (A), primitive intestine (B), chorionic villi (C) and chondrocytes of the disc (D), mesenchymal cells and chondrocytes of the limb (E), and the skin (E arrow). In contrast, no CAIX expression was seen in the CNS (A), primitive intestine (B), and chorionic villi (C). Co-expression of HIF-1α and CAIX was seen in the skin (E) and the cells involved in chondrogenesis (D, E). During later human development, around 19–20 weeks, HIF-1α expression was persistently observed in the kidney (F) and rectum (G) but no CAIX expressing cells were seen in these organs. However, a degree of overlap between CAIX and HIF-1α expression was seen in the skin (H), squamous mucosa of the vagina and the cervix (I and J). W = gestational age in weeks. Original magnifications: A, B, D-H (40×); C (left panel 20×; right panel 40×); I (20×); J (left panel 20×; right panel 40×).
Mentions: Recent evidence indicates that the fetus exists in a relatively hypoxic environment. The fetal PO2 is 35 mm of Hg compared with 100 mm of Hg in the adult [23]. HIF-1α mRNA is constitutively expressed in all organs and at all stages of gestation from 14–22 weeks, with the highest expression noted in the brain, heart, kidney, lung and liver [23]. However, HIF-1α protein is rapidly degraded in the proteasome, via VHL E3 ligase recognition, under normoxic conditions and is stabilized under hypoxic conditions [2,3]. In the transgenic mouse model study conducted by Provot et al., they found that HIF-1α protein is stably expressed and transcriptionally active in limb bud mesenchyme and in mesenchyme condensations during fetal development [24]. Thus, HIF-1 appears to play an important role in early chondrogenesis and joint formation. We performed an immunohistochemical study for HIF-1α expression on the fetal tissues, representing all stages of human development from 5–38 weeks of gestation, and encompassing both embryonic and fetal development. We found that as early as 5–9 weeks of gestation, diffuse HIF-1α nuclear immunoreactivity was seen in most of the embryonic and fetal tissues, particularly in the endothelial cells, body mesenchymal cells and nervous system (Fig. 8A), primitive gastrointestinal tract (Fig. 8B), and the chondrocytes and mesenchyme of vertebral disc/limb bud (Fig. 8D, 8E). In the skin, HIF-1α expression was consistently observed during fetal development (Fig. 8E, 8H). Interestingly, the immature chorionic villi during the 1st trimester also showed diffuse HIF-1α nuclear staining (Fig. 8C) and this observation is consistent with that previously published [26]. Variable degrees of HIF-1α expression were also observed in the visceral organs, especially during 17–25 weeks of gestation. The best examples are shown in fig 8F (kidney) and 8G (rectum). Although HIF-1α expression was persistent throughout the fetal period, the numbers of expressing cells progressively diminished. During the last trimester of fetal development (27–40 weeks) stable HIF-1α expression was limited to chondrocytes, endothelial cells, skin, and epithelial cells of the squamous mucosa, such as the vagina and cervix (Fig. 8I, 8J), the oral cavity, esophagus and anus.

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