دورية أكاديمية

Deficiency of Pdcd10 causes urothelium hypertrophy and vesicle trafficking defects in ureter.

التفاصيل البيبلوغرافية
العنوان: Deficiency of Pdcd10 causes urothelium hypertrophy and vesicle trafficking defects in ureter.
المؤلفون: Yixuan Wang, Baotao Ma, Youli Jian, Shi-Ting Wu, Wong, Alex, Wong, Justin, Bonder, Edward M., Xiangjian Zheng
المصدر: FEBS Journal; Mar2024, Vol. 291 Issue 5, p1008-1026, 19p
مصطلحات موضوعية: UROTHELIUM, KERATINOCYTE differentiation, URETERS, ORGANELLE formation, BUD development, GENE expression
مستخلص: The scaffolding protein programmed cell death protein 10 (Pdcd10) has been demonstrated to play a critical role in renal epithelial cell homeostasis and function by maintaining appropriate water reabsorption in collecting ducts. Both ureter and kidney collecting duct systems are derived from the ureter bud during development. Here, we report that cadherin-16 (Cdh16)- cre drives gene recombination with high specificity in the ureter, but not the bladder, urothelium. The consequences of Pdcd10 deletion on the stratified ureter urothelium were investigated using an integrated approach including messenger RNA (mRNA) expression analysis, immunocytochemistry, and high-resolution confocal and electron microscopy. Loss of Pdcd10 in the ureter urothelium resulted in increased expression of uroplakins (Upks) and keratins (Krts), as well as hypertrophy of the ureter urothelium with an associated increase in the number of proliferation marker protein Ki-67 (Ki67)-expressing cells specifically within the basal urothelium layer. Ultrastructural analysis documented significant modification of the intracellular membrane system, including intracellular vesicle genesis and transport along the basal- to umbrella-cell-layer axis. Additionally, Pdcd10 loss resulted in swelling of Golgi compartments, disruption of mitochondrial cristae structure, and increased lysosomal fusion. Lack of Pdcd10 also resulted in decreased fusiform vesicle formation in umbrella cells, increased secretion of exosome vesicles, and alteration in microvillar structure on apical membranes. Our findings indicate that Pdcd10 expression and its influence on homeostasis is associated with modulation of endomembrane trafficking and organelle biogenesis in the ureter urothelium. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:1742464X
DOI:10.1111/febs.17022