Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1 −/− Mice by Regulating Macrophage M2 Polarization

AbstractAdult autosomal dominant polycystic kidney disease (ADPKD) has been shown to be related as a “third hit” to the occurrence of acute or chronic kidney injury. Here, we examined whether dehydration, as a common kidney risk factor, could cause cystogenesis in chronic-onsetPkd1−/− mice by regulating macrophage activation. First, we confirmed that dehydration accelerated cytogenesis inPkd1−/− mice and that macrophages infiltrated the kidney tissues even earlier than macroscopic cyst formation. Then, microarray analysis suggested that glycolysis pathway may be involved in macrophage activation inPkd1−/− kidneys under conditions of dehydration. Further, we confirmed glycolysis pathway was activated and lactic acid (L-LA) was overproduced in thePkd1−/− kidney under conditions of dehydration. We have already proved that L-LA strongly stimulated M2 macrophage polarization and overproduction of polyamine in macrophagein vitro, and in the present study, we further discovered that M2 polarization-induced polyamine production shortened the primary cilia length by disrupting the PC1/PC2 complex. Finally, the activation of L-LA –arginase 1–polyamine pathway contributed to cystogenesis and progressive cyst growth inPkd1−/− mice recurrently exposed to dehydration.

Source: Inflammation - July 22, 2023 Category: Allergy & Immunology Source Type: research