Storm Tina, Christensen Erik I, Christensen Julie Nelly, Kjaergaard Tine, Uldbjerg Niels, Larsen Agnete, Honoré Bent, Madsen Mette
Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
Department of Clinical Medicine-Obstetrics and Gynaecology, Aarhus University Hospital, Skejby, Denmark (NU).
J Histochem Cytochem. 2016 Dec;64(12):769-784. doi: 10.1369/0022155416672210. Epub 2016 Oct 21.
The membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly proliferative cells in placenta. Only limited amounts of megalin could be detected in syncytiotrophoblasts and least in term placenta syncytiotrophoblasts. Immunocytochemical analyses furthermore showed that placental megalin associates with structures of the endolysosomal apparatus. Combined, our results clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream, as previously proposed. In contrast, our results point toward novel and complex functions for megalin in the cytotrophoblasts. Thus, we propose that the perception of placental megalin localization and function should be revised.
膜受体巨蛋白对胎儿正常发育至关重要。除了在发育中的胎儿中表达外，巨蛋白在人胎盘中也有表达。与其在肾近端小管中已确定的功能相似，胎盘巨蛋白被认为可介导重要营养物质的摄取。然而，巨蛋白在人胎盘中的表达、亚细胞定位及功能细节仍有待确定。通过对孕早期和足月人胎盘进行免疫组织化学分析，我们发现巨蛋白主要在细胞滋养层细胞中表达，细胞滋养层细胞是胎盘中高度增殖的细胞。在合体滋养层细胞中只能检测到少量巨蛋白，在足月胎盘合体滋养层细胞中含量最少。免疫细胞化学分析还表明，胎盘巨蛋白与内溶酶体装置的结构相关。综合来看，我们的结果清楚地表明胎盘巨蛋白与配体的内吞作用和运输有关。然而，由于巨蛋白在合体滋养层细胞中表达有限，尤其是在足月胎盘中，因此胎盘巨蛋白的主要作用似乎并非如先前提出的那样介导从母体血液中摄取营养物质。相反，我们的结果表明巨蛋白在细胞滋养层细胞中具有新的复杂功能。因此，我们建议应重新认识胎盘巨蛋白的定位和功能。
