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Glomerular disease due to podocyte malfunction is a major factor in the pathogenesis of chronic kidney disease. Identification of podocyte-specific signaling pathways is therefore a prerequisite to characterizing relevant disease pathways and developing novel treatment approaches. Here, we employed loss of function studies for EPB41L5 (Yurt) as a central podocyte gene to generate a cell type-specific disease model. Loss of Yurt in fly nephrocytes caused protein uptake and slit diaphragm defects. Transcriptomic and proteomic analysis of human EPB41L5 knockout podocytes demonstrated impaired mechanotransduction via the YAP/TAZ signaling pathway. Further analysis of specific inhibition of the YAP/TAZ-TEAD transcription factor complex by TEADi led to the identification of ARGHAP29 as an EPB41L5 and YAP/TAZ-dependently expressed podocyte RhoGAP. Knockdown of ARHGAP29 caused increased RhoA activation, defective lamellipodia formation, and increased maturation of integrin adhesion complexes, explaining similar phenotypes caused by loss of EPB41L5 and TEADi expression in podocytes. Detection of increased levels of ARHGAP29 in early disease stages of human glomerular disease implies a novel negative feedback loop for mechanotransductive RhoA—YAP/TAZ signaling in podocyte physiology and disease.

Exposure to a wide variety of chemicals can pose significant hazards to patients, and present health care professionals with scenarios that require proper assessment and treatment. Knowing when a chemical exposure requires emergency medical attention is equally as important as knowing when such assistance is not necessary and that simple treatment measures performed at home will suffice. This current discussion is intended to highlight selected principles and clinical information pertaining to common chemical exposures, but not to replace the full spectrum of information that would be available to health care professionals (and the lay public) by contacting their nearest poison control center. There are several factors that should be considered when assessing the nature of and possible clinical outcomes (and medical needs) from patient exposure to chemicals. Identification of the chemical(s) involved, events leading up to the exposure, route of exposure (e.g., ingestion, dermal, inhalation, ocular), patient medical history and current symptoms, are just a few of the variables that must be ascertained before various treatment approaches can be undertaken.