Yue Liang, Kajino Kazunori, Kobayashi Toshiyuki, Sugitani Yoshinobu, Sugihara Masami, Kakuta Soichiro, Harada Norihiro, Sasano Hitoshi, Kojima Masataka, Abe Masaaki, Lu Rong, Otsuji Naomi, Orimo Akira, Hino Okio
Department of Molecular Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Department of Human Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Int J Mol Sci. 2025 May 2;26(9):4330. doi: 10.3390/ijms26094330.
In adults, expressed in renal cancer (ERC)/mesothelin is exclusively expressed in the mesothelial cells lining the pleural, pericardial, and peritoneal cavities, yet its function under physiological conditions is unknown. To explore this, we studied ERC expression in wild-type (WT) mice at different developmental stages by immunohistochemistry and analyzed the ultrastructure of the mesothelium in WT and -knockout (KO) mice via electron microscopy. Additionally, cardiopulmonary function in adult WT and -KO mice was assessed using echocardiography and the forced oscillation technique (FOT). During embryonic development in WT mice, ERC expression was detected in the epicardium as early as embryonic day (E)12.5 but was absent in the pleura until E18.5. The timing of expression appeared to coincide with the active maturation of these organs, which implied a potential role in cardiopulmonary development. Electron microscopy revealed that microvilli on the mesothelium of -KO mice were immature compared to those of WT mice. Based on these findings, we hypothesized that ERC might contribute to cardiopulmonary function; however, echocardiography and FOT did not reveal any functional differences between WT and -KO mice. This suggests that ERC has limited functional relevance under physiological conditions.
在成年人中,肾癌中表达的间皮素(ERC)仅在胸膜、心包膜和腹膜腔的间皮细胞中表达,但其在生理条件下的功能尚不清楚。为了探究这一点,我们通过免疫组织化学研究了野生型(WT)小鼠在不同发育阶段的ERC表达,并通过电子显微镜分析了WT和基因敲除(KO)小鼠间皮的超微结构。此外,使用超声心动图和强迫振荡技术(FOT)评估了成年WT和KO小鼠的心肺功能。在WT小鼠的胚胎发育过程中,早在胚胎第(E)12.5天就在心外膜中检测到了ERC表达,但直到E18.5天胸膜中才出现。表达时间似乎与这些器官的活跃成熟相吻合,这暗示了其在心肺发育中的潜在作用。电子显微镜显示,与WT小鼠相比,KO小鼠间皮上的微绒毛不成熟。基于这些发现,我们推测ERC可能对心肺功能有贡献;然而,超声心动图和FOT并未揭示WT和KO小鼠之间的任何功能差异。这表明在生理条件下,ERC的功能相关性有限。