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Glomerular visceral epithelial cells (i.e., podocytes) are an essential component of the tripartite glomerular filtration barrier. Healthy podocytes are terminally differentiated cells with limited replicative capacity; however, inappropriate cell cycle reentry can be induced in podocytes by various injurious stimuli. In this issue of the JCI, Yamaguchi et al. report on a somatic mosaic gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit (p110α, encoded by PIK3CA). The study reveals that activating mutations of p110α can drive podocyte proliferation in PIK3CA-related overgrowth syndrome (PROS). They also showed that selective, small-molecule inhibitors of p110 may be useful for the treatment of proliferative glomerulonephritis. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-1 receptor type 1 (IL-1R1) activation triggers a proinflammatory signaling cascade that can exacerbate kidney injury. However, the functions of podocyte IL-1R1 in glomerular disease remain unclear. To study the role of IL-1R1 signaling in podocytes, we selectively ablated podocyte IL-1R1 in mice (PKO mice). We then subjected PKO mice and wild-type controls to two glomerular injury models: nephrotoxic serum (NTS)- and adriamycin-induced nephropathy. Surprisingly, we found that IL-1R1 activation in podocytes limited albuminuria and podocyte injury during NTS- and adriamycin-induced nephropathy. Moreover, deletion of IL-1R1 in podocytes drove podocyte apoptosis and glomerular injury through diminishing Akt activation. Activation of Akt signaling abrogated the differences in albuminuria and podocyte injury between wild-type and PKO mice during NTS. Thus, IL-1R1 signaling in podocytes limits susceptibility to glomerular injury via an Akt-dependent signaling pathway. These data identify an unexpected protective role for IL-1R1 signaling in podocytes in the pathogenesis of glomerular disease. [ABSTRACT FROM AUTHOR]

The National Academies of Science stresses the importance of research mentoring. We assessed the internal consistency and application of a novel 33 item mentor evaluation survey and explored differences across subgroups. The survey was administered annually to mentees. The response rate was 17.8% for a sample of 710 respondents. The survey exhibited strong internal validity with Cronbach Alpha > 0.89 for each subscale. Overall scores across the three domains were high. Basic Science trainees scored their mentor significantly lower than those in Translational or Clinical Science across domains (0.11-0.25 points). Underrepresented Racial Ethnic Groups (UREG) trainee scores were significantly lower in academic guidance and personal communication. Women had lower scores in 4 out of 5 domains. The survey is a modified instrument to assess mentee experience, although further validation against mentee outcomes is needed.