The double-edged sword role of TGF-β signaling pathway between intrauterine inflammation and cranial neural crest development.
Haiyang LiDenglu LongGuohua LvXin ChengGuang WangXuesong YangPublished in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2022)
Intrauterine infection would harm a developing embryo/fetus, thereby increasing the risk of developmental malformation. But, whether or not the infection-induced inflammation affects neural crest development still remains obscure. In this study, we employed meta-analysis to demonstrate the potential correlation between infection-induced inflammation and craniofacial anomalies, which was usually derived from the problems in neural crest cell development. The correlation was further verified by inflammatory cytokine release and the activation of nuclear factor kappa-light-chain enhancer of activated B cells signaling in lipopolysaccharide-treated HH10 chicken embryos. In such an inflammatory condition, AP-2α- and Pax7-labeled pre-migratory and migratory neural crest cells in HH10 chicken embryos were significantly less than the ones in control. The bioinformatics analysis of RNA-seq data demonstrated that the principal differential gene expression occurred in transforming growth factor-beta (TGF-β) signaling pathway, which was confirmed by the subsequent experimental results of quantitative PCR and immunofluorescent staining. Under this inflammatory circumstance, whole-mount in situ hybridization, immunofluorescence, and quantitative PCR showed the gene expression changes of key EMT-related transcription factors including upregulated Msx1, downregulated Slug, and FoxD3, as well as adhesion molecules and extracellular matrix protein including upregulated Cadherrin6B, E-cadherin, N-cadherin, and Laminin at the dorsal portion of neural tube of HH10 chicken embryos. Meanwhile, the bioinformatics analysis of RNA-seq data also manifested the differential gene expressions relevant to cell proliferation, which was confirmed by proliferating cell nuclear antigen Western blot data and co-immunofluorescence staining of human natural killer-1 and phosphorylated histone H3. In brief, this study revealed for the first time that the double-edged sword role of TGF-β signaling pathway between intrauterine inflammation (protective role) and cranial neural crest development (harmful role).
Keyphrases
- rna seq
- single cell
- transforming growth factor
- epithelial mesenchymal transition
- oxidative stress
- signaling pathway
- gene expression
- nuclear factor
- induced apoptosis
- diabetic rats
- transcription factor
- pi k akt
- extracellular matrix
- cell proliferation
- systematic review
- electronic health record
- dna methylation
- toll like receptor
- high glucose
- big data
- endothelial cells
- spinal cord
- mental health
- cell therapy
- randomized controlled trial
- spinal cord injury
- risk assessment
- genome wide
- cystic fibrosis
- stem cells
- south africa
- mass spectrometry
- pseudomonas aeruginosa
- endoplasmic reticulum stress
- immune response
- newly diagnosed
- mesenchymal stem cells
- machine learning
- genome wide identification
- artificial intelligence
- neuropathic pain
- copy number