FIGURE 4.

Role of non-receptor tyrosine-protein kinase 1 (TNK1) in hemorrhage-induced kidney injury. TNK1 expression and cellular apoptosis were analyzed in kidneys from non-human primates (A–C). (A) TNK1 was stained by immunohistochemistry (TNK1 staining in red; nuclei were counterstained with hematoxylin) in non-human primate kidneys after hemorrhagic shock with placebo treatment (HS) or HS and treatment with the complement inhibitor Cp40 (HS + Cp40) as well as in healthy control animals (Ctrl). Quantification of stained tissues revealed a significant increase in TNK1 expression in HS animals compared to controls which was abolished by Cp40 treatment (B). A TUNEL assay showed similar results with a significant increase in apoptotic events in kidneys after hemorrhage which was prevented by complement blockade using Cp40 (C); *p < 0.05, n = 3 Ctrl, n = 4 HS, n = 4 HS + Cp40 for (B,C). In murine distal convoluted tubule cells (D,E), TNK1 expression was significantly increased after stimulation with interleukin 6 (IL-6), but not altered after incubation with activated complement component 3 (C3a), or lipopolysaccharide (LPS, D). Cellular permeability for 4 kDa FITC-labeled dextran in a transwell chamber was significantly increased after stimulation with IL-6, but not with C3a or LPS (E). The data in (D) and (E) are representative of two independent experiments. *p < 0.05, n = 5 for (D,E).