Department of Anatomy, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.
Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia.
Int J Mol Sci. 2024 Jun 21;25(13):6829. doi: 10.3390/ijms25136829.
The purpose of this study was to evaluate the spatiotemporal immunoexpression pattern of microtubule-associated protein 1 light chain 3 beta (LC3B), glucose-regulated protein 78 (GRP78), heat shock protein 70 (HSP70), and lysosomal-associated membrane protein 2A (LAMP2A) in normal human fetal kidney development (CTRL) and kidneys affected with congenital anomalies of the kidney and urinary tract (CAKUT). Human fetal kidneys (control, horseshoe, dysplastic, duplex, and hypoplastic) from the 18th to the 38th developmental week underwent epifluorescence microscopy analysis after being stained with antibodies. Immunoreactivity was quantified in various kidney structures, and expression dynamics were examined using linear and nonlinear regression modeling. The punctate expression of LC3B was observed mainly in tubules and glomerular cells, with dysplastic kidneys displaying distinct staining patterns. In the control group's glomeruli, LAMP2A showed a sporadic, punctate signal; in contrast to other phenotypes, duplex kidneys showed significantly stronger expression in convoluted tubules. GRP78 had a weaker expression in CAKUT kidneys, especially hypoplastic ones, while normal kidneys exhibited punctate staining of convoluted tubules and glomeruli. HSP70 staining varied among phenotypes, with dysplastic and hypoplastic kidneys exhibiting stronger staining compared to controls. Expression dynamics varied among observed autophagy markers and phenotypes, indicating their potential roles in normal and dysfunctional kidney development.
本研究旨在评估微管相关蛋白 1 轻链 3β（LC3B）、葡萄糖调节蛋白 78（GRP78）、热休克蛋白 70（HSP70）和溶酶体相关膜蛋白 2A（LAMP2A）在正常人类胎儿肾脏发育（CTRL）和先天性肾和尿路异常（CAKUT）中的时空免疫表达模式。对第 18 至 38 周发育周的人类胎儿肾脏（对照、马蹄形、发育不良、双肾盂和发育不全）进行荧光显微镜分析，并用抗体染色。在各种肾脏结构中定量测定免疫反应性，并使用线性和非线性回归模型检查表达动态。LC3B 的点状表达主要观察到在肾小管和肾小球细胞中，发育不良的肾脏显示出明显的染色模式。在对照组的肾小球中，LAMP2A 显示出散在的点状信号；与其他表型相比，双肾盂在卷曲小管中表现出明显更强的表达。GRP78 在 CAKUT 肾脏中的表达较弱，尤其是发育不全的肾脏，而正常肾脏的卷曲小管和肾小球呈现点状染色。HSP70 的染色在不同的表型之间存在差异，发育不良和发育不全的肾脏与对照组相比表现出更强的染色。观察到的自噬标志物和表型之间的表达动态存在差异，表明它们在正常和功能失调的肾脏发育中的潜在作用。
