Journal: eLife
Article Title: JAK-STAT pathway activation compromises nephrocyte function in a Drosophila high-fat diet model of chronic kidney disease
doi: 10.7554/eLife.96987
Figure Lengend Snippet: Nephrocytes from control Drosophila ( w 1118 ; 7-day-old females) fed a regular diet (normal fat diet, NFD) or high-fat diet (NFD supplemented with 14% coconut oil, HFD), with or without methotrexate (10 μM; ex vivo 60 min) treatment. ( A ) Representative confocal images of FITC-albumin fluorescence (green). Scale bar: 50 μm. ( B ) Box plot shows the quantitation of the relative fluorescence intensity of FITC-albumin uptake based on images in ( A ); middle line depicts the median and whiskers show minimum to maximum. Statistical analysis was performed by two-way ANOVA with Sidak correction; *** p <0.001, **** p <0.0001; ns, not significant; n=6 flies (7-day-old females). ( C ) Representative confocal images of 10 kD dextran fluorescence (red). Scale bar: 50 μm. ( D ) Box plot shows the quantitation of the relative fluorescence intensity of 10 kD dextran uptake based on images in ( C ); middle line depicts the median and whiskers show minimum to maximum. Statistical analysis was performed by two-way ANOVA with Sidak correction; **** p <0.0001; ns, not significant; n=6 flies (7-day-old females). ( E ) Graphic of proposed model for high-fat diet-induced nephrocyte defects via an adipose-nephrocyte axis. A high-fat diet upregulates the expression and secretion of the adipokine Unpaired 2 (Upd2), leptin-like hormone, from the fat body. Upd2 is a Janus kinase/signal transducer and activator of transcription (JAK-STAT) ligand, and it activates JAK-STAT signaling at the nephrocytes (Signal-transducer and activator of transcription 92E, Stat92E; Suppressor of cytokine signaling at 36E, Socs36E; JAK Hopscotch, Hop; Domeless, Dome). The overactive JAK-STAT pathway disrupts the integrity of the slit diaphragm (SD) filtration structure and thereby leads to nephrocyte dysfunction.
Article Snippet: The dorsal cuticle (with nephrocytes) was transferred to methotrexate solution (10 μM) in Schneider’s Drosophila Medium (Thermo Fisher Scientific, MA) and incubated at room temperature for 60 min.
Techniques: Control, Ex Vivo, Fluorescence, Quantitation Assay, Expressing, Filtration