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Xingfei DAI, Qitang LI, Rongshuang YAN, Qingdong ZHANG, Cheng PAN, Derui FEI, Yujian MA, Shixin XU, Ying ZHANG. Molecular Analysis on the Molecular Mechanism of Lung Development in the Piglet Model of Early Onset Scoliosis Complicated with Thoracic Insufficiency Syndrome[J]. Journal of Kunming Medical University.
Citation: Xingfei DAI, Qitang LI, Rongshuang YAN, Qingdong ZHANG, Cheng PAN, Derui FEI, Yujian MA, Shixin XU, Ying ZHANG. Molecular Analysis on the Molecular Mechanism of Lung Development in the Piglet Model of Early Onset Scoliosis Complicated with Thoracic Insufficiency Syndrome[J]. Journal of Kunming Medical University.

Molecular Analysis on the Molecular Mechanism of Lung Development in the Piglet Model of Early Onset Scoliosis Complicated with Thoracic Insufficiency Syndrome

  • Received Date: 2024-01-16
    Available Online: 2024-04-30
  •   Objective  To identify key HUB genes involved in lung development through transcriptomic sequencing and bioinformatics analysis using tissue samples collected from an established piglet model of early-onset scoliosis with thoracic insufficiency syndrome (EOS+TIS) and its treatment model.   Methods  EOS+TIS and treatment animal models were established, followed by histological analysis using HE and Masson staining to observe lung tissue morphology and fibrosis severity. Lung tissue samples from three groups (control, model, treatment) were sequenced. Differential analysis was performed using the DESeq2 package in R, and differential gene GO/KEGG enrichment analysis was conducted using the DAVID database. Core genes were identified, relevant pathways were predicted, and validation was done via PCR and Western blot experiments.   Results  (1) HE staining results: The model group displayed significant bronchopulmonary dysplasia, which was notably improved in the treatment group. (2) Masson staining results: The model group showed severe lung fibrosis, which was alleviated in the treatment group. (3) DESeq2 analysis: The normal vs. model group comparison identified 170 upregulated and 262 downregulated genes, while the model vs. treatment group comparison identified 323 upregulated and 467 downregulated genes. (4) GO functional annotation: Differential genes were mainly enriched in functions like extracellular matrix, plasma membrane composition, immune response, inflammatory response, calcium ion binding, and cytokine activity. KEGG enrichment: Differential genes were primarily enriched in pathways like neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction. (5) Common gene identification: THBS1 was identified as a common gene. (6) PCR and Western Blot validation: THBS1 was downregulated in the model group and upregulated post-treatment (P < 0.05). Western Blot analysis revealed that TGF-β expression was reduced in the model group and increased post-treatment (P < 0.05).  Conclusion  THBS1 and TGF-β are involved in the process of lung development in the early onset scoliosis with thoracic insufficiency syndrome pig models.
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