Target for Ischemia-Reperfusion Injury
More than 13 million people are affected by acute kidney injury. Thereby, kidney function drops severely within a few days or weeks. Each year, 1.7 million people die from it worldwide. Unfortunately, one of the main causes of acute kidney injury (AKI) is renal ischemia-reperfusion injury.
Renal causes of AKI include disease or damage to the kidney. The disorders may involve the blood vessels, small vascular or nerve tangles (glomeruli), the renal tubules (tubules) or the interstitium. Diseases of the glomeruli can be inflammatory or the result of vascular damage due to ischemia. Similarly, the tubules may be affected by ischemia as well.
Overexpression of PIM1 protects against renal ischemia-reperfusion injury
Now, a new study appearing in International Immunopharmacology in January 2023 shows: PIM1 has a protective effect on renal IRI, and the underlying mechanism may be related to the ASK1-JNK/P38 pathway. What exactly is PMI1? PIM1, also known as Pim-1 proto-oncogene, serine/threonine kinase, is a protein that plays a role in regulating cell death and survival. This is done by phosphorylating various substrates within cells. PIM1 has been implicated in the development of several types of cancer, and some studies have suggested that it may be a potential therapeutic target for treating certain diseases.
In this study, we inhibited or overexpressed PIM1 in mice and cultured proximal tubular cells, and then induced renal IRI model in vivo and hypoxia reoxygenation (HR) model in vitro. Renal function, renal structure injuries and cellular death were assessed to reflect the extent of IRI. The expression of PIM1 and the levels of ASK1, MAPK and their phosphorylated forms were detected by immunoblot. RNA sequencing of kidney cortex was performed to analyze downstream pathway of PIM1 in renal IRI.
The authors found that PIM1 expression is upregulated in renal IRI and that overexpression of PIM1 protects against renal IRI by inhibiting ASK1 activity, thereby increasing phosphorylation at Ser83, which in turn blocks the JNK/P38 pathway. Moreover, inhibition of PIM1 exacerbated renal IRI, and the authors noted that PIM1 regulated IRI through the ASK1-JNK/P38 pathway. These findings suggest that PIM1 may be a potential therapeutic target for treating renal IRI.