A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina

Moon, Sohyun; Lee, Sangmi; Caesar, Joy Ann; Pruchenko, Sarah; Leask, Andrew; Knowles, James A.; Sinon, Jose; Chaqour, Brahim

doi:10.1016/j.isci.2020.101184

Cited by 41 publications

(26 citation statements)

References 88 publications

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“…YAP promotes the germination and remodeling of neovascules through various angiogenesis factors such as Ang2, MMP2, VE-cadherin, α‐SMA, and PGC1α [ 68 , 69 ]. Knockout of the YAP reduces vascular density, budding, and branching [ 70 ]. In addition, it is reported that mutation of YAP significantly promoted alveolar budding [ 69 ].…”

Section: The Hippo Signaling Pathway and Respiratory Diseasesmentioning

confidence: 99%

Hippo signaling pathway and respiratory diseases

Tang

Yangzhong

et al. 2022

Cell Death Discov.

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The hippo signaling pathway is a highly conserved evolutionary signaling pathway that plays an important role in regulating cell proliferation, organ size, tissue development, and regeneration. Increasing evidences consider that the hippo signaling pathway is involved in the process of respiratory diseases. Hippo signaling pathway is mainly composed of mammalian STE20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), WW domain of the Sav family containing protein 1 (SAV1), MOB kinase activator 1 (MOB1), Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ), and members of the TEA domain (TEAD) family. YAP is the cascade effector of the hippo signaling pathway. The activation of YAP promotes pulmonary arterial vascular smooth muscle cells (PAVSMCs) proliferation, which leads to pulmonary vascular remodeling; thereby the pulmonary arterial hypertension (PAH) is aggravated. While the loss of YAP leads to high expression of inflammatory genes and the accumulation of inflammatory cells, the pneumonia is consequently exacerbated. In addition, overexpressed YAP promotes the proliferation of lung fibroblasts and collagen deposition; thereby the idiopathic pulmonary fibrosis (IPF) is promoted. Moreover, YAP knockout reduces collagen deposition and the senescence of adult alveolar epithelial cells (AECs); hence the IPF is slowed. In addition, hippo signaling pathway may be involved in the repair of acute lung injury (ALI) by promoting the proliferation and differentiation of lung epithelial progenitor cells and intervening in the repair of pulmonary capillary endothelium. Moreover, the hippo signaling pathway is involved in asthma. In conclusion, the hippo signaling pathway is involved in respiratory diseases. More researches are needed to focus on the molecular mechanisms by which the hippo signaling pathway participates in respiratory diseases.

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Section: The Hippo Signaling Pathway and Respiratory Diseasesmentioning

confidence: 99%

Hippo signaling pathway and respiratory diseases

Tang

Yangzhong

et al. 2022

Cell Death Discov.

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“…Consistent with this, we confirmed that Hippo-signaling is affected in Rab40c-KO cells by TAZ immunostaining and qRT-PCR quantification of YAP/TAZ target genes. More interestingly, a recent study showed that Rab40c is down-regulated upon YAP stimulation ( Moon et al, 2020 ), thus the Rab40c-PP6 and YAP/TAZ may constitute a feed-forward loop to regulate FAs dynamics in migrating cells. Taken together, our data suggest that the Cul5/Rab40c-ANKRD28/PP6 axis is an important regulator of Hippo-signaling and FAs dynamics ( Fig 8G ).…”

Section: Discussionmentioning

confidence: 99%

Rab40c regulates focal adhesions and PP6 activity by controlling ANKRD28 ubiquitylation

et al. 2022

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Rab40c is a SOCS box–containing protein which binds Cullin5 to form a ubiquitin E3 ligase complex (Rab40c/CRL5) to regulate protein ubiquitylation. However, the exact functions of Rab40c remain to be determined, and what proteins are the targets of Rab40c-Cullin5–mediated ubiquitylation in mammalian cells are unknown. Here we showed that in migrating MDA-MB-231 cells Rab40c regulates focal adhesion’s number, size, and distribution. Mechanistically, we found that Rab40c binds the protein phosphatase 6 (PP6) complex and ubiquitylates one of its subunits, ankyrin repeat domain 28 (ANKRD28), thus leading to its lysosomal degradation. Furthermore, we identified that phosphorylation of FAK and MOB1 is decreased in Rab40c knock-out cells, which may contribute to focal adhesion site regulation by Rab40c. Thus, we propose a model where Rab40c/CRL5 regulates ANKRD28 ubiquitylation and degradation, leading to a decrease in PP6 activity, which ultimately affects FAK and Hippo pathway signaling to alter focal adhesion dynamics.

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“…An extensive body of evidences suggests that angiogenesis is temporally coordinated with the barriergenesis ( Engelhardt and Liebner, 2014 ; Umans et al., 2017 ), Prnd is involved in blood vessel development and endothelial barrier integrity in the CNS ( Chen et al., 2020 ), and CTGF participates in both retinal angiogenesis and BBB ( Moon et al., 2020 ). Neurons and glia also play important roles in coupled angiogenesis and barriergenesis ( Biswas et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%