Volume 45 Issue 5
May  2024
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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, 2024, 45(5): 49-59. doi: 10.12259/j.issn.2095-610X.S20240508
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, 2024, 45(5): 49-59. doi: 10.12259/j.issn.2095-610X.S20240508

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

doi: 10.12259/j.issn.2095-610X.S20240508
  • Received Date: 2024-01-16
    Available Online: 2024-04-30
  • Publish Date: 2024-05-31
  •   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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  • [1]
    Campbell R M Jr,Smith M D,Mayes T C,et al. The characteristics of thoracic insufficiency syndrome associated with fused ribs and congenital scoliosis[J]. J Bone Joint Surg Am,2003,85(3):399-408.
    [2]
    Cooney T P,W M Thurlbeck. The radial alveolar count method of emery and mithal: A reappraisal 2-intrauterine and early postnatal lung growth[J]. Thorax,1982,37(8):580-583. doi: 10.1136/thx.37.8.580
    [3]
    Dogar A M,Semplicio G,Guennewig B,et al. Multiple microRNAs derived from chemically synthesized precursors regulate thrombospondin 1 expression[J]. Nucleic Acid Ther,2014,24(2):149-159. doi: 10.1089/nat.2013.0467
    [4]
    Harpel J G,Schultz-Cherry S,Murphy-Ullrich J E,et al. Tamoxifen and estrogen effects on TGF-beta formation: Role of thrombospondin-1,alphavbeta3,and integrin-associated protein[J]. Biochem Biophys Res Commun,2001,284(1):11-14. doi: 10.1006/bbrc.2001.4922
    [5]
    Bissinger R,Petkova-Kirova P,Mykhailova O,et al. Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance,survival,and deformability of human red blood cells[J]. Cell Commun Signal,2020,18(1):155. doi: 10.1186/s12964-020-00651-5
    [6]
    Grosser J A,Maes M E,Nickells R W. Characteristics of intracellular propagation of mitochondrial BAX recruitment during apoptosis[J]. Apoptosis,2021,26(1-2):132-145. doi: 10.1007/s10495-020-01654-w
    [7]
    Jiang D,Guo B,Lin F,et al. Effect of THBS1 on the biological function of hypertrophic scar fibroblasts[J]. Biomed Res Int,2020,2020(1):8605407.
    [8]
    Lai Y H,Lee P Y,Lu C Y,et al. Thrombospondin 1-induced exosomal proteins attenuate hypoxia-induced paraptosis in corneal epithelial cells and promote wound healing[J]. FASEB J,2021,35(1):e21200.
    [9]
    陈冲,封志纯. 支气管肺发育不良分子遗传学研究进展[J]. 实用儿科临床杂志,2012,27(16):1282-1284.
    [10]
    Inui N,Sakai S,Kitagawa M. Molecular pathogenesis of pulmonary fibrosis,with focus on pathways related to TGF-β and the ubiquitin-proteasome pathway[J]. Int J Mol Sci,2021,22(11):6107. doi: 10.3390/ijms22116107
    [11]
    Chanda D,Otoupalova E,Smith S R,et al. Developmental pathways in the pathogenesis of lung fibrosis[J]. Mol Aspects Med,2019,65(1):56-69. doi: 10.1016/j.mam.2018.08.004
    [12]
    Lawler J,Miao W M,Duquette M,et al. Thrombospondin-1 gene expression affects survival and tumor spectrum of p53-deficient mice[J]. Am J Pathol,2001,159(5):1949-1956. doi: 10.1016/S0002-9440(10)63042-8
    [13]
    Zippel N,Malik R A,Fromel T,et al. Transforming growth factor-beta-activated kinase 1 regulates angiogenesis via AMP-activated protein kinase-alpha1 and redox balance in endothelial cells[J]. Arterioscler Thromb Vasc Biol,2013,33(12):2792-2799.
    [14]
    Xu S,Yang S,Sun G,et al. Transforming growth factor-beta polymorphisms and serum level in the development of osteosarcoma[J]. DNA Cell Biol,2014,33(1):802-806. doi: 10.1089/dna.2014.2527
    [15]
    Rashid A,Zeng C,Motta-Ribeiro G,et al. Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions[J]. Sci Rep,2022,12(1):7065. doi: 10.1038/s41598-022-11045-7
    [16]
    Kaneshita S,Kida T,Yoshioka M,et al. CG223,a novel BET inhibitor,exerts TGF-β1-mediated antifibrotic effects in a murine model of bleomycin-induced pulmonary fibrosis[J]. Pulm Pharmacol Ther,2021,70(2):102057. doi: 10.1016/j.pupt.2021.102057
    [17]
    Wang I M,Stepaniants S,Boie Y,et al. Gene expression profiling in patients with chronic obstructive pulmonary disease and lung cancer[J]. Am J Respir Crit Care Med,2008,177(4):402-411. doi: 10.1164/rccm.200703-390OC
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