Role of renal urothelium in the development and progression of kidney disease

Abstract

The clinical and financial impact of chronic kidney disease (CKD) is significant, while the progression and prognosis of CKD is variable and often poor. Studies using the megabladder (mgb−/−) model of CKD have shown that renal urothelium plays a key role in modulating the early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical and molecular characterization of Upk1bRFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/AUM formation and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in the normal development and pathogenesis of the urinary tract, and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression.

Effective expression analysis using gene interaction matrices and convolutional neural networks

“…For example, the top 30 important gene interactions for Kidney Renal Clear Cell Carcinoma naturally, and perhaps surprisingly, fall into a well-connected network with UPK1B, GPX2, and AQP4 representing the top three hubs, all of which have been linked to renal cancer. For instance, the top connected gene, UPK1B has recently emerged as an essential gene for renal urothelium function 9 , and is a known promoter of bladder metastasis 10 . GPX2, a renal cancer-promoting gene, manifests high expression in specific clinical sub-types only 11 , highlighting the feature of GIM-CNNs in extracting meaningful links that are challenging for typical DEG-based approaches.…”

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway

“…This protein is found in asymmetric unit membranes and can interact with other family members to form complexes. And this complex may function in normal bladder epithelial physiology to regulate membrane permeability of superficial umbrella cells or stabilize the apical membrane through AUM/cytoskeleton interactions [ 29 ]. High expression of UPK1B in clinical samples of bladder cancer was highly correlated with lymph node metastasis, distant metastasis and advanced stage of tumor.…”

Identification of pathogenic genes associated with CKD: An integrated bioinformatics approach

“…Chronic kidney disease (CKD) is considered among the major types of nephrosis across the globe, with a successive increase in its associated patients in recent years ( Epstein et al, 1988 ; Carpenter and McHugh, 2017 ). CKD is a highly heterogeneous disease, wherein kidney structure and function are damaged ( Webster et al, 2017 ; Tonelli et al, 2006 ; De Nicola and Zoccali, 2016 ; Guo et al, 2019 ; Wilson et al, 2021 ).…”

“…CKD is categorized into a five distinct stages on the basis of the glomerular filtration rate (GFR), i.e., G1 (GFR ≥ 90 ml/min/1.73 m 2 ), G2 (GFR 60–89 ml/min/1.73 m 2 ), G3a (45–59 ml/min/1.73 m 2 ), G3b (30–44 ml/min/1.73 m 2 ), G4 (15–29 ml/min/1.73 m 2 ), and G5 ( Kidney International Supplements, 2013 ). The early CKD stages ( Epstein et al, 1988 ; Carpenter and McHugh, 2017 ), show few symptoms, and the disease is not detected till it reaches later stages ( Rajapurkar et al, 2012 ). The rate of morbidity and mortality increases with the succession of CKD stages.…”