👤 Astrid Klooster

Dyslipidemia is an important risk factor in CKD. The liver clears triglyceride-rich lipoproteins (TRL) Uninephrectomy- and aging-induced CKD in normotensive Wistar rats and hypertensive Munich-Wistar-Frömter (MWF) rats. Compared with 22-week-old sex- and strain-matched rats, 48-week-old uninephrectomized Wistar-CKD and MWF-CKD rats showed proteinuria, increased plasma creatinine, and hypercholesterolemia (all Progressive CKD induces hepatic HS elongation, leading to increased interaction with PCSK9. This might reduce hepatic lipoprotein uptake and thereby induce dyslipidemia in CKD. Therefore, PCSK9/HS may be a novel target to control dyslipidemia. Show less

Mutations in the human Crumbs homologue-1 (CRB1) gene cause retinal diseases including Leber's congenital amaurosis (LCA) and retinitis pigmentosa type 12. The CRB1 transmembrane protein localizes at a subapical region (SAR) above intercellular adherens junctions between photoreceptor and Müller glia (MG) cells. We demonstrate that the Crb1-/- phenotype, as shown in Crb1-/- mice, is accelerated and intensified in primary retina cultures. Immuno-electron microscopy showed strong Crb1 immunoreactivity at the SAR in MG cells but barely in photoreceptor cells, whereas Crb2, Crb3, Patj, Pals1 and Mupp1 were present in both cell types. Human CRB1, introduced in MG cells in Crb1-/- primary retinas, was targeted to the SAR. RNA interference-induced silencing of the Crb1-interacting-protein Pals1 (protein associated with Lin7; Mpp5) in MG cells resulted in loss of Crb1, Crb2, Mupp1 and Veli3 protein localization and partial loss of Crb3. We conclude that Pals1 is required for correct localization of Crb family members and its interactors at the SAR of polarized MG cells. Show less