Claudin domain containing 1 contributing to endothelial cell adhesion decreases in presence of cerebellar hemorrhage

Abstract

The claudin family comprises four-pass transmembrane proteins involved in the formation of tight junctions (TJs). Relatively recently, claudin domain containing (CLDND) 1, also known as claudin-25, was identified as a novel member of the claudin family. In the present study, we revealed that in the adult murine brain, CLDND1 is abundant in the cerebellum among common sites of intracerebral hemorrhage. Thus, the dynamics of CLDND1 after cerebellar hemorrhage were examined. Both CLDND1 mRNA and protein levels transiently decreased at 24 hr after hemorrhagic insult. For immunostaining, an anti-CLDND1 antibody that recognizes the specific epitope in the extracellular first loop was prepared. Dual immunohistochemical staining with CD31 using coronal cryosections of intact murine cerebellum tissue revealed that CLDND1 is expressed on endothelial cells. We therefore performed an in vitro permeability test using a human brain endothelial cell (HBEC) line to reveal whether CLDND1 contributes to cell adhesion like other claudins. CLDND1 was expressed on HBECs as well as in murine cerebellum tissue, and a strong signal was observed at TJs. RNA interference against CLDND1 decreased both the mRNA and protein levels without cytotoxicity. The permeability to small molecules, but not to large ones, across confluent HBECs increased on CLDND1 knockdown compared with mock-treated cells. These results suggest that the transient decrease of CLDND1 after cerebellar hemorrhage is responsible for low-molecular-weight selective vascular hyperpermeability. © 2017 Wiley Periodicals, Inc.

Retinoic acid receptor-related orphan receptor α reduces lipid droplets by upregulating neutral cholesterol ester hydrolase 1 in macrophages

“…In brain endothelial cells, claudin domain containing 1 (CLDND1), which is involved in tight junction formation, is regulated at the transcriptional level by RORα and at the post-transcriptional level by miR-124 [29,30]. Moreover, decreased CLDND1 expression in the adult murine cerebellum results in cerebellar hemorrhage [31].…”

Lovastatin Suppresses the Transcriptional Regulation of <i>CLDND1</i> in Human Hepatoma Cells

“…11) CLDND1 expression was reduced in a mouse model of cerebellar hemorrhage, and knockdown of CLDND1 in human brain endothelial cells resulted in an enhanced vascular permeability. 13) These results suggest that decreased expression of CLDND1 causes cerebral hemorrhage in the cerebellum. As most of the cholesterol is synthesized in the liver in vivo, liver cells are considered to be less affected by lovastatin than other cell types.…”

“…11) A previous study using a mouse model of cerebellar hemorrhage reported that the expression of CLDND1 is downregulated during cerebellar hemorrhage, and CLDND1 knockdown in human vascular endothelial cells resulted in an enhanced vascular permeability. 13) Therefore, we hypothesized that insufficient transcriptional regulation of CLDND1 by RORα is associated with the pathogenesis of cerebrovascular conditions such as cerebral hemorrhage. However, the transcriptional regulation of CLDND1 has not been studied extensively to date, and the effect of cholesterol on the RORα-mediated transcriptional regulation of CLDND1 remains unknown.…”

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families

“…Of interest is the DIOPT‐derived prediction (although with a low score) that the claudin domain‐containing 1 gene ( cldnd1 ) represents the human ortholog of all three proteins. The contribution of cldnd1 (alias for cldn25 in Mus musculus ) in cell adhesion has been examined in the adult mouse brain where the transient decrease in cldnd1 was found to induce selective vascular hyperpermeability after cerebellar haemorrhage 125 …”