Retinal blood vessel‐origin yes‐associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF)

Autor: Xi Chen, Liqianyu Ai, Rongdi Yuan, Jian Ye, Jingyi Zhu, Sen Lin, Zhou Zhang, Jun Yan, Wenyi Liu, Chunlin Chen, Yun-Jia Liu
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Angiogenesis
medicine.medical_treatment
Leukemia Inhibitory Factor
Mice
chemistry.chemical_compound
0302 clinical medicine
Neovascularization
Pathologic
Glial fibrillary acidic protein
biology
Chemistry
Cell Differentiation
General Medicine
yes‐associated protein
Cell biology
Endothelial stem cell
medicine.anatomical_structure
astrocyte premature
030220 oncology & carcinogenesis
Female
Original Article
Astrocyte
Neurogenesis
Neovascularization
Physiologic
Cre recombinase
Retina
03 medical and health sciences
leukaemia inhibitory factor
Glial Fibrillary Acidic Protein
Coactivator
medicine
Animals
Humans
Adaptor Proteins
Signal Transducing
Cell Proliferation
Growth factor
Endothelial Cells
Retinal Vessels
YAP-Signaling Proteins
Retinal
Original Articles
Cell Biology
Coculture Techniques
Mice
Inbred C57BL
030104 developmental biology
Astrocytes
biology.protein
retinal vessel development
Transcription Factors
Zdroj: Cell Proliferation
ISSN: 1365-2184
0960-7722
Popis: Objectives To testify that endothelial cells (ECs) induce astrocyte maturation by leukaemia inhibitory factor (LIF) secretion. Materials and Methods In vivo experiments, mice bearing floxed alleles of YAP were crossed with mice expressing a Cre recombinase driven by the endothelial Tek promoter (Tek‐Cre) to finally obtain the following three genotypes: YAP f/f, Tek‐Cre; YAP f/w, Tek‐Cre; and YAP f/f. Retinal vascularization and astrocyte network were evaluated by whole‐mount fluorescence and Western blotting. In vitro, experiments were performed in an astrocyte and human microvascular endothelial cell (HMEC‐1) coculture model to analyse the mechanisms underlying the effect of endothelial YAP on astrocytes. Results In vivo, YAPf/f;Tek‐Cre mice showed delayed angiogenesis, sparse vessels and decreased glial fibrillary acidic protein (GFAP)+ astrocytes but aberrant growth of endothelial networks and immature astrocytes (platelet‐derived growth factor A, PDGFRA+ astrocytes) overgrowth. In vitro, Yap deletion attenuated the LIF release that delayed the maturation of retinal astrocyte which was consistent with the results of HMEC‐1—astrocyte coculture. The effect of YAP overexpression on LIF‐LIFR axis in HMEC‐1 interferes the GFAP expression of astrocyte. In contrast, LIF protein rescues the astrocytic GFAP expression when EC YAP was inhibited by siRNAs. Conclusions We show that EC yes‐associated protein (YAP) is not only a critical coactivator of Hippo signalling in retinal vessel development but also plays an essential role in retinal astrocyte maturation by regulating LIF production.
Databáze: OpenAIRE
Externí odkaz: