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Introduction The epithelium of the stomach corpus is organized into clonal units that are surrounded by myosin heavy chain 11-expressing ([MYH11.sup.+]) stromal cells. These units contain multiple differentiated cell types [...], The stomach corpus epithelium is organized into anatomical units that consist of glands and pits. Mechanisms that control the cellular organization of corpus glands and enable their recovery upon injury are not well understood. R-spondin 3 (RSPO3) is a WNT-signaling enhancer that regulates stem cell behavior in different organs. Here, we investigated the function of RSPO3 in the corpus during homeostasis, upon chief and/or parietal cell loss, and during chronic Helicobacter pylori infection. Using organoid culture and conditional mouse models, we demonstrate that RSPO3 is a critical driver of secretory cell differentiation in the corpus gland toward parietal and chief cells, while its absence promoted pit cell differentiation. Acute loss of chief and parietal cells induced by high dose tamoxifen--or merely the depletion of [LGR5.sup.+] chief cells caused an upregulation of RSPO3 expression, which was required for the initiation of a coordinated regenerative response via the activation of yes-associated protein (YAP) signaling. This response enabled a rapid recovery of the injured secretory gland cells. However, in the context of chronic H. pylori infection, the R-spondin-driven regeneration was maintained long term, promoting severe glandular hyperproliferation and the development of premalignant metaplasia.

Dent’s disease is characterized by manifestations of proximal tubule dysfunction including hypercalciuria, kidney stones, proteinuria, rickets and progressively declining kidney function. The diagnosis is based on the presence of low-molecular-weight proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, kidney stones, haematuria, hypophosphataemia or renal insufficiency. Dent’s disease is a hereditary condition that is caused by variants in the CLCN5 gene or the OCRL1 gene and affects only males. Herein, we report on two brothers who were found to have a previously reported disease-causing variant in the CLCN5 gene. One sibling had nephrocalcinosis, proteinuria and hypercalciuria, whereas the other sibling was asymptomatic and had normal laboratory findings. [ABSTRACT FROM AUTHOR]

Influenza can cause significant morbidity and mortality in renal transplant recipients especially with a high rate of lower respiratory disease. Annual influenza vaccination is therefore recommended to renal transplant recipients. We report the first three cases of acute kidney injury in renal transplant recipients following influenza vaccination that all led to graft loss. They all had different native diseases and were all vaccinated in the same season of 2009-10. The time span from vaccination to decline of kidney function is shorter than the time to diagnosis since the three patients only had blood tests every 3 months or when symptoms became severe. These reports do not justify a change of current recommendations regarding influenza vaccination in renal transplant recipients, but they support the continued attention and registration of vaccinations to monitor side effects. [ABSTRACT FROM AUTHOR]

Cells that lack p53 signaling frequently occur in ulcerative colitis (UC) and are considered early drivers in UC-associated colorectal cancer (CRC). Epithelial injury during colitis is associated with transient stem cell reprogramming from the adult, homeostatic to a "fetal-like" regenerative state. Here, we use murine and organoid-based models to study the role of Trp53 during epithelial reprogramming. We find that p53 signaling is silent and dispensable during homeostasis but strongly up-regulated in the epithelium upon DSS-induced colitis. While in WT cells this causes termination of the regenerative state, crypts that lack Trp53 remain locked in the highly proliferative, regenerative state long-term. The regenerative state in WT cells requires high Wnt signaling to maintain elevated levels of glycolysis. Instead, Trp53 deficiency enables Wnt-independent glycolysis due to overexpression of rate-limiting enzyme PKM2. Our study reveals the context-dependent relevance of p53 signaling specifically in the injury-induced regenerative state, explaining the high abundance of clones lacking p53 signaling in UC and UC-associated CRC.