Human PIM1 adenoviral particles

Cisplatin is a potent anticancer drug that often causes acute kidney injury (AKI) by inducing mitochondrial damage. PIM1 is a serine/threonine kinase that has been shown to regulate mitochondrial function. Here, researchers found that PIM1 was activated in cisplatin-induced AKI in vivo and cisplatin-induced renal tubular cell injury in vitro. PIM1 inhibition aggravated cisplatin-induced AKI in vivo, whereas PIM1 overexpression attenuated cisplatin-induced renal injury in vivo and in vitro. Furthermore, PIM1 inhibition exacerbated mitochondrial injury in mice, but PIM1 overexpression attenuated mitochondrial injury in mice and BUMPT cells. In mice and BUMPT cells, PIM1 inhibition downregulated the expression of p-Drp1S637, whereas PIM1 overexpression upregulated the expression of p-Drp1S637. Inhibition of Drp1 activity attenuated cellular injury in BUMPT cells with knockdown or inhibition of PIM1. These studies suggest that PIM1 has a protective effect against cisplatin-induced AKI, and regulation of Drp1 activation may be the underlying mechanism. Therefore, PIM1 may be a potential therapeutic target for cisplatin-induced AKI.

To investigate the role of PIM1 in regulating mitochondrial function in vitro, the researchers infected BUMPT cells with adenovirus expressing PIM1. The transfection efficiency was then verified by Western Blot (Figure 1A). After completing PIM1 adenovirus infection and cisplatin treatment, the researchers examined cell apoptosis by flow cytometry, and the results showed that PIM1 overexpression reduced cisplatin-induced cell apoptosis (Figure 1B-C). The expression of Cleaved-Caspase3 in PIM1 overexpressing cells was consistently reduced compared with negative control cells (Figure 1E). These data reflect that PIM1 overexpression reduces cisplatin-induced tubular cell apoptosis. Next, the researchers measured intracellular ATP and ROS levels in BUMPT cells. Cisplatin treatment reduced intracellular ATP levels (Figure 1D) and caused overproduction of ROS (Figure 1F-G), and the results showed that PIM1 overexpressing cells had higher intracellular ATP levels (Figure 1D) and lower ROS production (Figure 1F-G) compared with negative control cells. In addition, cisplatin treatment led to a decrease in the ratio, while PIM1 overexpression reversed this effect (Figure 1E). Confocal microscopy results showed that mitochondria were fragmented after cisplatin treatment (Figure 1H-I), and PIM1 overexpression alleviated cisplatin-induced mitochondrial fragmentation (Figure 1H-I). Taken together, these results indicate that PIM1 overexpression can alleviate cisplatin-induced tubular injury and mitochondrial dysfunction in vitro.

Figure 1. PIM1 overexpression reduced cisplatin-induced tubular injury and mitochondrial dysfunction in BUMPT cells. (Li Y, et al., 2024)