Proximal tubule cell migration is likely a critical early event in recovery from acute renal injury with spreading and migration of cells to cover denuded basement membrane. Growth factors (GFs), including epidermal (EGF), hepatocyte (HGF) and insulin-like growth factor-1 (IGF-1), may play an important role in repair. We have previously shown that each stimulates migration in immortalized human proximal renal tubule cells under control conditions. We now investigated the effect of GFs on migration of these cells after oxidant stress. The cells were cultured in serum- and growth factor-free medium. Confluent cultures were exposed to H2O2 for 1 hour, washed, then scraped with a pipette tip. GFs were added and the area of migration was measured over the next 6 hours. After oxidant stress with 750 μM peroxide, migration decreased to 60% of control (uninjured, no GFs) values. After EGF and HGF migration returned nearly to control values while IGF-1 actually stimulated migration to 131 ± 12 (SEM) % of control values. Adding EGF or HGF to IGF-1 further stimulated migration to 163 ± 16% and 166 ± 13% of control values respectively, representing an increase of ˜ 2.7× over peroxide injured cells (with no GFs). EGF and HGF were not additive. With more severe injury (1.2-1.5 mM H2O2), there was modest stimulation by HGF and IGF-1. There was still some additivity of EGF and HGF with IGF-1, averaging ˜ 1.5× peroxide alone, but values remained depressed compared to uninjured cells not treated with GFs. In summary, the GFs examined stimulated human proximal tubule cell migration after oxidant stress, with IGF-1 being the most potent, especially in combination with EGF or HGF. The stimulation was most pronounced with mild injury. We conclude that the stimulation of migration by growth factors may contribute to their beneficial effect after acute injury.
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