Publications by authors named "J A Hurcombe"
Diabetic kidney disease (DKD) is the leading cause of end stage kidney failure worldwide, of which cellular insulin resistance is a major driver. Here, we study key human kidney cell types implicated in DKD (podocytes, glomerular endothelial, mesangial and proximal tubular cells) in insulin sensitive and resistant conditions, and perform simultaneous transcriptomics and proteomics for integrated analysis. Our data is further compared with bulk- and single-cell transcriptomic kidney biopsy data from early- and advanced-stage DKD patient cohorts.
View Article and Find Full Text PDFInsulin signaling to the glomerular podocyte via the insulin receptor (IR) is critical for kidney function. In this study we show that near-complete knockout of the closely related insulin-like growth factor 1 receptor (IGF1R) in podocytes is detrimental, resulting in albuminuria and podocyte cell death . In contrast, partial podocyte IGF1R knockdown confers protection against doxorubicin-induced podocyte injury.
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- - The study investigates the mechanisms behind Shiga toxin-producing E. coli hemolytic uremic syndrome (STEC-HUS), a leading cause of acute kidney injury in children, revealing that the glomerular microvasculature is particularly vulnerable to damage from systemic Stx infection.
- - Researchers engineered mice to express the Stx receptor in kidney cells and found that exposure led to reduction of a crucial growth factor (VEGF-A), causing more damage via complement pathway activation.
- - The findings suggest that early intervention using a C5 inhibitor could be a promising treatment to mitigate the effects of STx-induced HUS, enhancing understanding of the disease's targeting of the kidneys.
Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte.
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- Scientists found that a drug called AZD5438 can help protect mitochondria, which are like power stations in our cells, from damage caused by another substance called CCCP.
- They discovered that AZD5438 was better at keeping these power stations healthy compared to other similar drugs.
- Tests on brain cells showed that AZD5438 not only kept the cells alive but also helped them work better, making it a promising option for future treatments.