Role of pericytes in the development of cerebral cavernous malformations.

ABSTRACT: Cerebral cavernous malformation (CCM) is caused by loss-of-function mutations in CCM1, CCM2, or CCM3 genes of endothelial cells. It is characterized by pericyte deficiency. However, the role of pericytes in CCMs is not yet clarified. We found pericytes in Cdh5Cre ^ERT2 ;Ccm1 ^fl/fl (Ccm1 ^ECKO ) mice had a high expression of PDGFRβ. The inhibition of pericyte function by CP-673451 aggravated the CCM lesion development. RNA-sequencing analysis revealed the molecular traits of pericytes, such as highly expressed ECM-related genes, especially Fn1. Furthermore, KLF4 coupled with phosphorylated SMAD3 (pSMAD3) promoted the transcription of fibronectin in the pericytes of CCM lesions. RGDS peptide,

SUBMITTER: Dai Z 

PROVIDER: S-EPMC9713377 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature