Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK Pathway.

Background B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear.Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy.Results Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1-promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy.Conclusions Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.

Short-term effect of back school based on cognitive behavioral therapy involving multidisciplinary collaboration.

ObjectivesThe purpose of this study was to develop a comprehensive back school program that included elements of CBT (Cognitive Behavioral Therapy), implement this through multidisciplinary collaboration, and ascertain its effectiveness as a pilot study. DesignThis school was implemented in the form of five 90-minute group sessions held every other week.MethodsParticipants comprised 7 chronic low back pain patients with poor improvement in the usual treatment. Practitioners were orthopaedic surgeon, physical therapist, and a clinical psychologist. This school contents were patient education, self-monitoring, back exercise, relaxation, stress management, cognitive restructuring, activity pacing, and exposure. ResultsFrom the Wilcoxon signed-rank test, each score of four scales or items (sense of control, PCS (pain catastrophizing), PASS-20 (escape/avoidance), FFD (finger-floor distance)) after this program significantly improved. Results of calculating the effect size, sense of control (d=0.55) is 'moderate', the PCS (d=1.12) and the PASS-20 (d=1.64) were 'large'.ConclusionsThis back school may be useful for physical function and psychological variables which much related to pain management and daily disabilities in patients with poor respond to standard orthopaedic treatment.