Skip to main content
. 2021 Nov 11;12:6537. doi: 10.1038/s41467-021-26900-w

Fig. 6. Orai1 inhibition protects podocyte foot processes and proteinuria.

Fig. 6

a Representative traces of fura-2 ratio and the images of bright-field and fura-2 fluorescence microscopy (upper panel) of podocytes, carried out in situ on the acutely isolated mouse in db/m and db/db mice treated with GSK-7975A (5 mg/kg/day for 1 month). b Summary of the SOCE in a. n = 20 (db/m + Vehicle), 22(db/db + Vehicle), and 17 (db/db + GSK) glomeruli per each group, respectively. c Effect of SOCE inhibitors on albuminuria. Twenty-four-hour urinary Alb/Cr ratio (left) and albumin excretion (right) were measured in db/m and db/db mice. Vehicle (PBS), GSK-7975A (GSK, 5 mg/kg/every 2 days) or 2-APB (2 mg/kg/every 2 days) were inoculated i.p. from 8 to 12 weeks. n = 7 (db/m + Veh), 4 (db/m + GSK), 5 (db/m + 2-APB), 5 (db/db + Veh), 5 (db/db + GSK), and 4 (db/db + 2-APB). d Representative immunoblots representing the effects of SOCE inhibitors, GSK-7975A (upper) or 2-APB (lower), on synaptopodin expression from db/m and db/db mice. e Summary of quantification in d. n = 4 mice each (left). n = 4 (db/m + Veh), 10 (db/m + 2-APB), 5 (db/db + Veh), and 7 (db/db + 2-APB) (right). f Rescue of synaptopodin depletion by SOCE inhibitors (GSK or 2-APB). Synaptopodin staining (green) of mouse glomeruli from db/m and db/db mice with or without GSK or 2-APB i.p. injection. Scale bar = 25 μm. g Analysis of the relative fluorescence intensity in f. n = 4 (db/db + Veh), 4 (db/db + Veh), 5 (db/db + GSK), and 6 (db/db + 2-APB). Thirty images from mice in each group. h Representative TEM images of the foot processes of the podocytes of SOCE inhibitor-treated db/db mice. Magnification is ×30,000. Scale bar = 1 μm. i, j Summary of GBM thickness (i) and an average number of foot processes per 1 μm length of GBM (j) in h. n = 4 (db/m + Veh), 10 (db/db + Veh), 6 (db/db + GSK), and 7 (db/db + 2-APB) thirty images from mice in each group. Data are expressed as mean ± SEM and were analyzed using two-way ANOVA followed by Tukey’s multiple comparisons test. *p < 0.05, **p < 0.01, ****p < 0.0001; ns not significant.