Mutations of CNTNAP1 led to defects in neuronal development

Li, Wanxing; Yang, Lin; Tang, Chuanqing; Liu, Kaiyi; Lu, Yulan; Wang, Huijun; Yan, Kai; Qiu, Zilong; Zhou, Wenhao

doi:10.1172/jci.insight.135697

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…APS is one of the most important post-transcriptional regulatory mechanisms involved in mRNA metabolism modulation, and its dysregulation has been implicated in many disease states [ 315 – 317 ]. A number of studies have reported a link between APA and fibrotic conditions including IPF [ 318 – 321 ]. Recently, Zhou et al reported that matrix stiffness induces cell fibrotic responses by a signaling mechanism involving the modulation of APA by the mammalian cleavage factor I (CFIm) [ 318 ].…”

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

“…A number of studies have reported a link between APA and fibrotic conditions including IPF [ 318 – 321 ]. Recently, Zhou et al reported that matrix stiffness induces cell fibrotic responses by a signaling mechanism involving the modulation of APA by the mammalian cleavage factor I (CFIm) [ 318 ]. These authors demonstrated that a stiff matrix acts as a down-regulator of the CFIm subunits CFIm68, CFIm59 and CFIm25, promoting the APA-dependent up regulation of collagen and fibronectin production in primary human lung fibroblasts [ 318 ].…”

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

“…Recently, Zhou et al reported that matrix stiffness induces cell fibrotic responses by a signaling mechanism involving the modulation of APA by the mammalian cleavage factor I (CFIm) [ 318 ]. These authors demonstrated that a stiff matrix acts as a down-regulator of the CFIm subunits CFIm68, CFIm59 and CFIm25, promoting the APA-dependent up regulation of collagen and fibronectin production in primary human lung fibroblasts [ 318 ]. In vivo experiments have also reported a strong association between matrix stiffness and CFIm subunits in a bleomycin-induced mouse model of pulmonary fibrosis [ 318 ].…”

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

“…These authors demonstrated that a stiff matrix acts as a down-regulator of the CFIm subunits CFIm68, CFIm59 and CFIm25, promoting the APA-dependent up regulation of collagen and fibronectin production in primary human lung fibroblasts [ 318 ]. In vivo experiments have also reported a strong association between matrix stiffness and CFIm subunits in a bleomycin-induced mouse model of pulmonary fibrosis [ 318 ]. By regulating APA, the CFIm subunit CFIm25 appears to play an essential role in fibroblast-to-myofibroblast differentiation [ 321 ].…”

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

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Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

239

152

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Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

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Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

See 2 more Smart Citations

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

239

152

View full text Add to dashboard Cite

show abstract

“…13 The contactin-associated protein 1 (CNTNAP1, also known as CASPR1) was originally identified as a vital cell-adhesion protein belonging to the neurexin superfamily. 14 CNTNAP1 participated in gap junction formation and neuronal development 15,16 as it can bind to Cntn1, 17 native prion protein, 18 and neurofascin. 19,20 Downregulated CASPR1 expression was related to the axonal demyelination in multiple sclerosis.…”

Section: Introductionmentioning

confidence: 99%

M2‐polarization‐related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma

Meng

et al. 2022

IUBMB Life

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Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies, characterized by high mortality rate in urology. Unfortunately, reliable biomarkers for ccRCC diagnosis and prognosis remain lacking. Contactin‐associated protein 1 (CNTNAP1) has yet to be thoroughly investigated in cancer, especially its relationship with immune infiltration or clinical outcomes of ccRCC. Here, we explored The Cancer Genome Atlas Kidney Clear Cell Carcinoma database (TCGA‐KIRC) for prognostic significance, differential expression, and probable mechanism of CNTNAP1. The aberrant CNTNAP1 expression was also validated by the International Cancer Genome Consortium (ICGC) and ccRCC clinic samples. We used Database for Annotation, Visualization, and Integrated Discovery to perform the GO and KEGG enrichment. TIMER database was further utilized to assess its correlation with immune infiltration in ccRCC. The CellMiner database was used to analyze the relationship between CNTNAP1 expression and drug sensitivity. Results showed CNTNAP1 was upregulated in TCGA‐KIRC, ICGC, and clinic samples. And CNTNAP1 expression was positively related to infiltration levels of cancer‐associated fibroblast, regulatory T cells, and myeloid‐derived suppressor cells, while negatively related to eosinophils. Furthermore, we observed CNTNAP1 was appreciably positively associated with alternatively activated macrophage (M2) in ccRCC. Finally, high CNTNAP1 expression was negatively correlated with nilotinib, crizotinib, eribulin mesylate, and vinorelbine. Collectively, these results strongly suggest that CNTNAP1 might act as an immunotherapeutic target and a promising novel biomarker for ccRCC.

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Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway

et al. 2021

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Objective The glucocorticoid receptor (GR) is a member of the nuclear receptor family that controls key biological processes in the cardiovascular system and has recently been shown to modulate Wnt signaling in endothelial cells. Wnt/β-catenin signaling has been demonstrated to be crucial in the process of angiogenesis. In the current study, we studied whether GR could regulate angiogenesis via the Wnt/β-catenin pathway. Approach and Resultsa Key components of the Wnt/β-catenin pathway were evaluated using quantitative PCR and Western blot in the presence or absence of GR. Enhanced angiogenesis was found in GR deficiency in vitro and confirmed with cell viability assays, proliferation assays and tube formation assays. Consistent with these in vitro findings, endothelial cell-specific GR loss GR in vivo promoted angiogenesis in both a hind limb ischemia model and sponge implantation assay. Results were further verified in a novel mouse model lacking endothelial LRP5/6, a key receptor in canonical Wnt signaling, and showed substantially suppressed angiogenesis using these same in vitro and in vivo assays. To further investigate the mechanism of GR regulation of Wnt signaling, autophagy flux was investigated in endothelial cells by visualizing auto phagolysosomes as well as by assessing P62 degradation and LC3B conversion. Results indicated that potentiated autophagy flux participated in GR-Wnt regulation. Conclusions Lack of endothelial GR triggers autophagy flux, leads to activation of Wnt/β-catenin signaling and promotes angiogenesis. There may also be a synergistic interaction between autophagy and Wnt/β-catenin signaling.

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Mutations of CNTNAP1 led to defects in neuronal development

Cited by 11 publications

References 45 publications

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

M2‐polarization‐related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma

Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway

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