关键词: CAKUT GRP78 HSP70 LAMP2A LC3B autophagy congenital anomalies of the kidney and urinary tract nephrogenesis

Mesh : Humans Endoplasmic Reticulum Chaperone BiP Autophagy Lysosomal-Associated Membrane Protein 2 / metabolism genetics Kidney / metabolism abnormalities pathology Microtubule-Associated Proteins / metabolism HSP70 Heat-Shock Proteins / metabolism Heat-Shock Proteins / metabolism Urogenital Abnormalities / metabolism pathology Urinary Tract / metabolism abnormalities Vesico-Ureteral Reflux / metabolism pathology

来  源:   DOI:10.3390/ijms25136829   PDF(Pubmed)

Abstract:
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.
摘要:
本研究的目的是评估微管相关蛋白1轻链3β(LC3B)的时空免疫表达模式,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)在正常人胎儿肾脏发育(CTRL)和患有先天性肾脏和泌尿道异常(CAKUT)的肾脏中。人类胎儿肾脏(对照,马蹄铁,发育不良,双工,和发育不全)从第18到第38周的发育周用抗体染色后进行了落射荧光显微镜分析。在各种肾脏结构中定量了免疫反应性,并使用线性和非线性回归模型检查表达动力学。LC3B的点状表达主要在肾小管和肾小球细胞中,发育不良的肾脏显示不同的染色模式。在对照组的肾小球中,LAMP2A显示出零星的,点状信号;与其他表型相比,双重肾脏在曲小管中显示出明显更强的表达。GRP78在CAKUT肾脏中表达较弱,尤其是发育不良的,而正常肾脏表现出曲小管和肾小球的点状染色。HSP70染色因表型而异,与对照组相比,发育不良和发育不良的肾脏表现出更强的染色。表达动力学在观察到的自噬标志物和表型之间有所不同,表明它们在正常和功能失调的肾脏发育中的潜在作用。
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