Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation

Zhang, Ji; Jiang, Xuheng; Zhang, Chao; Zhong, Jun; Fang, Xuanyu; Li, Huanhuan; Xie, Fangke; Huang, Xiaofei; Zhang, Xiaojun; Hu, Quan; Ge, Hongfei; Yu, Anyong

doi:10.1155/2020/4764012

Cited by 19 publications

(25 citation statements)

References 38 publications

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“…Myo broblasts play an important role in brosis, and α-SMA is activated in these cells. This indicator is involved in both cell migration and proliferation [38,39,40]. However, we found that PPP2R3A knockdown speci cally affected the brotic marker FN1 but had little effect on COL1 and α-SMA, suggesting that PPP2R3A may speci cally affect FN1 to cause brosis.…”

Section: Discussionmentioning

confidence: 92%

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

Shi¹,

Yang²,

Luo³

et al. 2021

Preprint

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Background: Fibroblasts have important roles in the synthesis and remodeling of extracellular matrix (ECM) proteins during pulmonary fibrosis. However, the spatiotemporal distribution of heterogeneous fibroblasts during disease progression remains unknown. Methods: Physiological saline and silica were used to generate a chronic pulmonary fibrosis model in mice, and single-cell sequencing, spatial transcriptome sequencing, real-time fluorescent quantitative PCR, immunohistochemistry and immunofluorescence were performed to identify fibroblast subtypes. Small interfering RNA was used to specifically knockdown the target protein, and western blotting, bromodeoxyuridine (BrdU), Cell Counting Kit-8 (CCK-8) and wound healing assays were used to detect the role of GREM1/PPP2R3A in a newly identified fibroblast subtype. Results: Fibroblasts of the new subtype were mainly located in the lesion area and coexpressed inflammation- and proliferation-related genes; they were termed inflammatory-proliferation fibroblasts. Grem1 was the most highly expressed gene in this subtype, as confirmed in HPF-a cells after TGF-β1 treatment. We characterized the downstream mechanism of GREM1/PPP2R3A: these factors mediated the increases in cell viability, proliferation and migration induced by TGF-β1 in fibroblasts. Conclusion: This new subtype of inflammatory, proliferative fibroblasts plays a pivotal role during pulmonary fibrosis, and PPP2R3A, as a downstream regulatory target of GREM1, is involved in pulmonary fibrosis, providing new insights for the prevention and treatment of silicosis.

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Section: Discussionmentioning

confidence: 92%

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

Shi¹,

Yang²,

Luo³

et al. 2021

Preprint

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“…The literature mining for these top hub DEGs identified many studies about their association with schizophrenia, psychiatric disorders or nervous system related functions (See Table S9 -3 for literature information). For example, ACTA2 is significantly downregulated in the postmortem cortex of schizophrenia patients ( Mladinov et al., 2016 ), and downregulation of ACTA2 inhibits neural stem cell migration ( Zhang et al., 2020 ). The deletion of 15q11-13, which covers gene ALDH1A2, is suggested to be involved schizophrenia ( Reay and Cairns, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…12 iScience 24, 103209, November 19, 2021 iScience Article (Zhang et al, 2020). The deletion of 15q11-13, which covers gene ALDH1A2, is suggested to be involved schizophrenia .…”

Section: Ll Open Accessmentioning

confidence: 99%

Systematic discovery of signaling pathways linking immune activation to schizophrenia

Gao

et al. 2021

iScience

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Summary Immune activation has been shown to play a critical role in the development of schizophrenia; however its underlying mechanism remains unknown. Our report demonstrates a high-quality protein interaction network for schizophrenia (SCZ Network), constructed using our “neighborhood walk” approach in combination with “random walk with restart”. The spatiotemporal expression pattern of the genes in this disease network revealed two developmental stages sensitive to perturbation by immune activation: mid-to late gestation, and adolescence. Furthermore, we induced immune activation at these stages in mice, carried out transcriptome sequencing on the mouse brains, and illustrated clear potential molecular pathways and key regulators correlating maternal immune activation during gestation and an increased risk for schizophrenia after a second immune activation at puberty. This work provides not only valuable resources for the study on molecular mechanisms underlying schizophrenia, but also a systematic strategy for the discovery of molecular pathways of complex mental disorders.

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“…Neuronal/glial and vascular markers are not mutually exclusive. For example, NPC express the smooth muscle marker SMA in mice which control their migration [ 48 ]. It was shown that OEC also express SMA and that the proportion of OEC simultaneously expressing SMA and GFAP grows with time of cultivation on the cell culture of model animals: rats, mice, hamsters, and monkeys [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Characterisation of Neurospheres-Derived Cells from Human Olfactory Epithelium

Zelenova

Kondratyev

Лежейко

et al. 2021

Cells

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A major problem in psychiatric research is a deficit of relevant cell material of neuronal origin, especially in large quantities from living individuals. One of the promising options is cells from the olfactory neuroepithelium, which contains neuronal progenitors that ensure the regeneration of olfactory receptors. These cells are easy to obtain with nasal biopsies and it is possible to grow and cultivate them in vitro. In this work, we used RNAseq expression profiling and immunofluorescence microscopy to characterise neurospheres-derived cells (NDC), that simply and reliably grow from neurospheres (NS) obtained from nasal biopsies. We utilized differential expression analysis to explore the molecular changes that occur during transition from NS to NDC. We found that processes associated with neuronal and vascular cells are downregulated in NDC. A comparison with public transcriptomes revealed a depletion of neuronal and glial components in NDC. We also discovered that NDC have several metabolic features specific to neuronal progenitors treated with the fungicide maneb. Thus, while NDC retain some neuronal/glial identity, additional protocol alterations are needed to use NDC for mass sample collection in psychiatric research.

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Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation

Cited by 19 publications

References 38 publications

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

Systematic discovery of signaling pathways linking immune activation to schizophrenia

Characterisation of Neurospheres-Derived Cells from Human Olfactory Epithelium

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