Conditioned Media of Choroid Plexus Epithelium Cells Attenuates High Pi-Induced Calcification of MOVAS Cells by Inhibiting ROS-Mediated Signal Pathways

Vascular calcification was an independent risk of cardiovascular and cerebrovascular diseases (CCDs). Studies reported that conditioned media of choroid plexus epithelium cells (CPECs-CM) showed potential neuroprotective effects. However, the protective effect of CPECs-CM against vascular calcification (VC) has not been reported yet. Herein, high phosphate (HPi)–induced calcification model in mouse aortic vascular smooth muscle cells (MOVAS) was established, and the protective effects and underlying mechanism of CPECs-CM against HPi-induced calcification were explored. The results indicated that CPEC cells were successfully isolated and cultured, and CPECs-CM co-treatment significantly inhibited HPi-induced calcification of MOVAS cells through blocking alkaline phosphatase activity and expression. CPECs-CM co-treatment also suppressed reactive oxide species–mediated DNA damage in HPi-treated MOVAS cells. Moreover, dysfunction of MAPKs and PI3K/AKT pathways both contributed to HPi-induced calcification of MOVAS cells, and CPECs-CM co-treatment attenuated HPi-induced calcification by normalizing MAPKs and PI3K/AKT expression. Taken together, our findings provide evidence that CPECs-CM had the potential to inhibit vascular calcification with potent application in chemoprevention and chemotherapy of human CCD.

NLRP3 inflammasome-mediated cerebrospinal fluid hypersecretion in choroid plexus contributes to hydrocephalus after hemorrhage

BackgroundHydrocephalus is a severe complication of intracerebral hemorrhage with ventricular extension (ICH-IVH). The choroid plexus epithelium plays an important role in cerebrospinal fluid (CSF) secretion and constitutes blood-CSF barrier adjusting brain–immune system interface. NLRP3 inflammasome is a key component of the innate system which promotes neuroinflammation. However, the role of NLRP3 inflammasome in the pathogenesis of hydrocephalus after hemorrhage has not been investigated.MethodsHydrocephalus after ICH-IVH rat model was accomplished by autologous blood infusion. Then, we investigated the relationship between NLRP3 inflammasome and CSF hypersecretion in choroid plexus.ResultsThe NLRP3 inflammasome activated and CSF hypersecretion in choroid plexus epithelium were found after ICH-IVH. NLRP3 inhibition with MCC950 decreased CSF secretion, ventricles dilation and attenuated neurofunction deficits after ICH-IVH. In addition, MCC950 decreased NKCC1 phosphorylation which was the major protein adjusting CSF secretion and improved blood-CSF barrier integrity after ICH-IVH.ConclusionsThis study demonstrates that NLRP3 inflammasome mediated CSF hypersecretion by influencing NKCC1 phosphorylation in choroid plexus epithelium plays an important role in the pathogenesis of hydrocephalus after hemorrhage and provides a new therapeutic strategy.

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.