Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia.
Department of Pediatric Surgery, University Hospital of Split, 21000 Split, Croatia.
Molecules. 2024 Jul 12;29(14):3294. doi: 10.3390/molecules29143294.
Kidney failures in infants are mostly caused by congenital anomalies of the kidney and urinary tract (CAKUT), which are among the most common congenital birth disorders worldwide when paired with cardiac abnormalities. People with CAKUT often have severe kidney failure as a result of a wide range of abnormalities that can occur alone or in conjunction with other syndromic disorders. In this study, we aimed to investigate the expression pattern of CAKUT candidate genes alpha-8 integrin (ITGA8) and Van Gogh-like 2 (VANGL2) in fetal tissues of healthy and CAKUT-affected kidneys using immunohistochemistry and immunofluorescence. We found that under CAKUT circumstances, the expressions of ITGA8 and VANGL2 are changed. Additionally, we showed that VANGL2 expression is constant during fetal aging, but ITGA8 expression varies. Moreover, compared to normal healthy kidneys (CTRL), ITGA8 is poorly expressed in duplex kidneys (DKs) and dysplastic kidneys (DYS), whereas VANGL2 is substantially expressed in dysplastic kidneys (DYS) and poorly expressed in hypoplastic kidneys (HYP). These results point to VANGL2 and ITGA8 as potential prognostic indicators for CAKUT malformations. Further research is necessary to explore the molecular mechanisms underlying this differential expression of ITGA8 and VANGL2.
婴儿肾衰竭主要由肾脏和泌尿道先天异常（CAKUT）引起，当与心脏异常同时发生时，CAKUT 是全球最常见的先天性出生缺陷之一。患有 CAKUT 的人通常由于广泛的异常而导致严重的肾衰竭，这些异常可以单独发生或与其他综合征疾病同时发生。在这项研究中，我们旨在使用免疫组织化学和免疫荧光法研究 CAKUT 候选基因α-8 整合素（ITGA8）和梵高样蛋白 2（VANGL2）在健康和 CAKUT 相关肾脏胎儿组织中的表达模式。我们发现，在 CAKUT 情况下，ITGA8 和 VANGL2 的表达发生了改变。此外，我们表明，VANGL2 表达在胎儿发育过程中是恒定的，而 ITGA8 表达则不同。此外，与正常健康肾脏（CTRL）相比，ITGA8 在双肾盂（DK）和发育不良肾脏（DYS）中表达较差，而 VANGL2 在发育不良肾脏（DYS）中大量表达，在发育不良肾脏（HYP）中表达较差。这些结果表明 VANGL2 和 ITGA8 可能是 CAKUT 畸形的潜在预后指标。需要进一步研究来探索 ITGA8 和 VANGL2 这种差异表达的分子机制。
