Liao Shu-Yuan, Lerman Michael I, Stanbridge Eric J
Department of Pathology, St. Joseph Hospital, Orange, CA, USA.
BMC Dev Biol. 2009 Mar 16;9:22. doi: 10.1186/1471-213X-9-22.
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.
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.
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.
跨膜碳酸酐酶IX（CAIX）和碳酸酐酶XII（CAXII）是α-碳酸酐酶（CA）家族的成员。它们在细胞分化、增殖和pH调节中起关键作用。CAIX和CAXII蛋白在肿瘤组织中的表达主要由缺氧诱导，对于CAIX尤其如此，它受转录因子缺氧诱导因子-1（HIF-1）调控。它们在正常成人组织中的分布仅限于并非总是处于缺氧状态的高度特化细胞。人类胎儿存在于相对缺氧的环境中。我们检测了发育中的人类胎儿和出生后组织中CAIX、CAXII和HIF-1α的表达，以确定CAIX和CAXII的表达是否仅受HIF-1调控。
CAIX和HIF-1α的共定位仅限于胚胎和早期胎儿组织中的某些细胞类型。这些细胞包括原始间充质或参与软骨形成和皮肤发育的细胞。CAIX的瞬时表达仅限于中胚层来源的未成熟组织以及皮肤和室管膜细胞。持续表达CAIX蛋白的唯一组织是体腔上皮（间皮）及其残余物、胃和胆管树的上皮、十二指肠和小肠中的腺体和隐窝细胞，以及位于那些先前被确定为例如皮肤和大肠中含有成体干细胞的部位的细胞。在许多情况下，CAIX和HIF-1α的共定位并不明显。CAXII的表达仅限于参与分泌和水吸收的细胞，如胃壁细胞、唾液腺和胰腺的腺泡细胞、大肠上皮和肾小管。未观察到CAXII与CAIX或HIF-1α的共定位。
该研究表明：1）HIF-1α和CAIX的表达在许多但并非所有胚胎和早期胎儿组织中共定位；2）没有证据表明CAIX和CAXII共定位；3）CAIX和CAXII的表达分别与细胞起源和涉及质子转运的分泌活性密切相关。在那些与干细胞龛相对应的部位发现罕见的表达CAIX的细胞这一有趣发现需要进一步研究。
