Hippo signaling pathway and respiratory diseases

Tang, Weifeng; Li, Min; Yangzhong, Xiaoting; Zhang, Xifeng; Zu, Anju; Hou, Yunjiao; Li, Lin; Sun, Shibo

doi:10.1038/s41420-022-01020-6

Cited by 31 publications

(27 citation statements)

References 118 publications

(191 reference statements)

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“…We observed overexpression of YAP mainly in hyperplastic epithelial alveolar cells, suggesting a role of the Hippo pathway in mediating the epithelial lung response after SARS-COV2 infection. Our results confirm and expand previous observations indicating that the Hippo signaling modulates alveolar regeneration after acute lung injury ( 30 ). During embryogenesis, YAP is expressed in progenitor basal cells and controls airway epithelial differentiation ( 31 , 32 ).…”

Section: Discussionsupporting

confidence: 92%

Progression to lung fibrosis in severe COVID-19 patients: A morphological and transcriptomic study in postmortem samples

Pérez-Míes

Caniego-Casas²,

Bardi³

et al. 2022

Front. Med.

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The development of lung fibrosis is a major concern in patients recovered from severe COVID-19 pneumonia. This study aimed to document the evolution of diffuse alveolar damage (DAD) to the fibrosing pattern and define the transcriptional programs involved. Morphological, immunohistochemical and transcriptional analysis were performed in lung samples obtained from autopsy of 33 severe COVID-19 patients (median illness duration: 36 days). Normal lung and idiopathic pulmonary fibrosis (IPF) were used for comparison. Twenty-seven patients with DAD and disease evolution of more than 2 weeks had fibrosis. Pathways and genes related with collagen biosynthesis and extracellular matrix (ECM) biosynthesis and degradation, myofibroblastic differentiation and epithelial to mesenchymal transition (EMT) were overexpressed in COVID-19. This pattern had similarities with that observed in IPF. By immunohistochemistry, pathological fibroblasts (pFBs), with CTHRC1 and SPARC expression, increased in areas of proliferative DAD and decreased in areas of mature fibrosis. Immunohistochemical analysis demonstrated constitutive expression of cadherin-11 in normal epithelial cells and a similar pattern of cadherin and catenin expression in epithelial cells from both normal and COVID-19 samples. Transcriptomic analysis revealed downregulation of the Hippo pathway, concordant with the observation of YAP overexpression in hyperplastic alveolar epithelial cells. Progression to fibrosis in severe COVID-19 is associated with overexpression of fibrogenic pathways and increased in CTHRC1- and SPARC-positive pFBs. Whereas the Hippo pathway seemed to be implicated in the response to epithelial cell damage, EMT was not a major process implicated in COVID-19 mediated lung fibrosis.

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Section: Discussionsupporting

confidence: 92%

Progression to lung fibrosis in severe COVID-19 patients: A morphological and transcriptomic study in postmortem samples

Pérez-Míes

Caniego-Casas²,

Bardi³

et al. 2022

Front. Med.

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“…Hippo signaling pathway is an evolutionally conserved pathway, which plays an important role in regulating cell proliferation, organ size, tissue development and regeneration (35). Accumulating evidence suggests the involvement of the Hippo pathway in fibrosis in various organs including lung, heart, pancreas and liver (36)(37)(38)(39). YAP1 is a transcriptional coactivator that is negatively regulated in the Hippo signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis

et al. 2022

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BackgroundDuring liver injury, liver sinusoidal endothelial cells (LSECs) dysfunction and capillarization promote liver fibrosis. We have previously reported that the LSEC vascular cell adhesion molecule 1 (VCAM1) plays a key role in liver inflammation in nonalcoholic steatohepatitis (NASH) and we now aim to uncover its role in LSEC capillarization and liver fibrosis.MethodsWild-type C57BL/6J mice were fed either chow or high fat, fructose and cholesterol diet to induce NASH and treated with either anti-VCAM1 neutralizing antibody or control isotype antibody. Inducible endothelial cell-specific Vcam1 deleted mice (Vcam1Δend) and control mice (Vcam1fl/fl) were fed choline-deficient high-fat diet (CD-HFD) to induce NASH or injected with carbon tetrachloride to induce liver fibrosis. LSECs isolated from Vcam1fl/fl or Vcam1Δend and hepatic stellate cells (HSCs) isolated from wild-type mice were cocultured in a 3-D system or a μ-Slide 2 well co-culture system.ResultsImmunostaining for Lyve1 (marker of differentiated LSECs) was reduced in Vcam1fl/fl mice and restored in Vcam1Δend mice in both NASH and liver fibrosis models. Co-immunostaining showed increased α-smooth muscle actin in the livers of Vcam1fl/fl mice in areas lacking Lyve1. Furthermore, scanning electron microscopy showed reduced LSEC fenestrae in the Vcam1fl/fl mice but not Vcam1Δend mice in both injury models, suggesting that VCAM1 promotes LSEC capillarization during liver injury. HSCs profibrogenic markers were reduced when cocultured with LSECs from CD-HFD fed Vcam1Δend mice compared to Vcam1fl/fl mice. Furthermore, recombinant VCAM1 activated the Yes-associated protein 1 pathway and induced a fibrogenic phenotype in HSCs in vitro, supporting the profibrogenic role of LSEC VCAM1.ConclusionVCAM1 is not just a scaffold for leukocyte adhesion during liver injury, but also a modulator of LSEC capillarization and liver fibrosis.

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“…Additionally, N. ceranae could also cause structural damage to midgut epithelial cells of A. mellifera ( Panek et al, 2018 ). The Hippo signaling pathway plays a crucial role in regulating cell proliferation as well as organ growth and regeneration ( Tang et al, 2022 ). Emerging evidence demonstrated the participation of the Hippo signaling pathway in the regulation of immune defense in mammals and insects ( Buchon et al, 2009 ; Hong et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

CircRNA-regulated immune responses of asian honey bee workers to microsporidian infection

et al. 2022

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Nosema ceranae is a widespread fungal parasite for honey bees, causing bee nosemosis. Based on deep sequencing and bioinformatics, identification of circular RNAs (circRNAs) in Apis cerana workers’ midguts and circRNA-regulated immune response of host to N. ceranae invasion were conducted in this current work, followed by molecular verification of back-splicing sites and expression trends of circRNAs. Here, 10185 and 7405 circRNAs were identified in the midguts of workers at 7 days (AcT1) and 10 days (AcT2) post inoculation days post-inoculation with N. ceranae. PCR amplification result verified the back-splicing sites within three specific circRNAs (novel_circ_005123, novel_circ_007177, and novel_circ_015140) expressed in N. ceranae-inoculated midgut. In combination with transcriptome data from corresponding un-inoculated midguts (AcCK1 and AcCK2), 2266 circRNAs were found to be shared by the aforementioned four groups, whereas the numbers of specific ones were 2618, 1917, 5691, and 3723 respectively. Further, 83 52) differentially expressed circRNAs (DEcircRNAs) were identified in AcCK1 vs. AcT1 (AcCK2 vs. AcT2) comparison group. Source genes of DEcircRNAs in workers’ midgut at seven dpi were involved in two cellular immune-related pathways such as endocytosis and ubiquitin mediated proteolysis. Additionally, competing endogenous RNA (ceRNA) network analysis showed that 23 13) DEcircRNAs in AcCK1 vs. AcT1 (AcCK2 vs. AcT2) comparison group could target 18 14) miRNAs and further link to 1111 (1093) mRNAs. These target mRNAs were annotated to six cellular immunity pathways including endocytosis, lysosome, phagosome, ubiquitin mediated proteolysis, metabolism of xenobiotics by cytochrome P450, and insect hormone biosynthesis. Moreover, 284 164) internal ribosome entry site and 54 26) ORFs were identified from DEcircRNAs in AcCK1 vs. AcT1 (AcCK2 vs. AcT2) comparison group; additionally, ORFs in DEcircRNAs in midgut at seven dpi with N. ceranae were associated with several cellular immune pathways including endocytosis and ubiquitin-mediated proteolysis. Ultimately, RT-qPCR results showed that the expression trends of six DEcircRNAs were consistent with those in transcriptome data. These results demonstrated that N. ceranae altered the expression pattern of circRNAs in A. c. cerana workers’ midguts, and DEcircRNAs were likely to regulate host cellular and humoral immune response to microsporidian infection. Our findings lay a foundation for clarifying the mechanism underlying host immune response to N. ceranae infection and provide a new insight into interaction between Asian honey bee and microsporidian.

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Hippo signaling pathway and respiratory diseases

Cited by 31 publications

References 118 publications

Progression to lung fibrosis in severe COVID-19 patients: A morphological and transcriptomic study in postmortem samples

Progression to lung fibrosis in severe COVID-19 patients: A morphological and transcriptomic study in postmortem samples

Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis

CircRNA-regulated immune responses of asian honey bee workers to microsporidian infection

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