B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis
Abstract
:1. Introduction
2. Results
2.1. B4GALT1 Gene Expression Is Increased in IPF and It Correlates with EMT Gene Pathway
2.2. Protein and Gene Expression Analysis in Primary Fibroblast Cell Cultures from IPF Patient
2.3. Protein Expression Analysis in Lung Speciemens from IPFpatients
2.4. Protein and Gene Expression Analysis in Patients with Fibrosis in Other Non-Lung Tissues
2.5. B4GALT1 Is Overexpressed in UIP/IPF Associated with Lung Cancer
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Bioinformatic Analysis
4.3. Primary Cell Cultures
4.4. RNA Extraction and Real Time RT-PCR
4.5. Immunofluorescence
4.6. Immunohistochemistry
4.7. Optical Microscopy
4.8. Statistical Analysis
4.9. Ethics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Pathways | p-Value | q-Value | Genes |
---|---|---|---|
Focal adhesion (WP306) | 3.54 × 10−28 | 1.04 × 10−25 | ITGB1, ITGB5, LAMA2, LAMA1, ITGB3, LAMA3, TNC, LAMC2, LAMC1, THBS2, THBS1, MYLK, COMP, SPP1, FLNA, ITGAV, PDGFRB, JUN, ITGA2, FN1, VEGFC, VEGFA, COL1A1, COL1A2, COL4A2, COL4A1, COL5A3, COL6A2, COL5A2, ITGA5, MYL9 |
miRNA targets in ECM and membrane receptors (WP2911) | 1.87 × 10−23 | 2.77 × 10−21 | ITGB5, FN1, LAMC1, THBS2, THBS1, COL3A1, COL1A2, COL5A1, COL4A2, COL4A1, COL5A3, COL6A2, COL5A2, COL6A3 |
Focal adhesion-PI3K-Akt-mTOR-signaling pathway (WP3932) | 1.93 × 10−22 | 1.89 × 10−20 | ITGB1, ITGB5, LAMA2, LAMA1, COL11A1, ITGB3, LAMA3, TNC, LAMC2, LAMC1, THBS2, FGF2, THBS1, COMP, SPP1, ITGAV, PDGFRB, ITGA2, FN1, VEGFC, VEGFA, COL1A1, COL3A1, COL1A2, COL4A2, COL5A1, COL4A1, COL5A3, COL6A2, COL5A2, ITGA5 |
PI3K-Akt signaling pathway (WP4172) | 7.67 × 10−19 | 5.65 × 10−17 | ITGB1, ITGB5, LAMA2, LAMA1, ITGB3, LAMA3, TNC, LAMC2, LAMC1, THBS2, FGF2, THBS1, COMP, SPP1, ITGAV, PDGFRB, BDNF, ITGA2, FN1, VEGFC, VEGFA, COL1A1, IL6, COL1A2, COL4A2, COL4A1, COL6A2, COL6A3, ITGA5 |
IL-18 signaling pathway (WP4754) | 4.42 × 10−16 | 2.60 × 10−14 | JUN, CXCL8, SDC4, MMP1, MMP2, MMP3, FN1, PLOD3, TNFAIP3, TNFRSF11B, VEGFA, COL1A1, ACTA2, MMP14, COL3A1, IL6, COL1A2, SPP1, TIMP3, FAS, PTX3, TIMP1, SNTB1, TGM2 |
Type I collagen synthesis in the context of osteogenesis imperfecta (WP4786) | 1.21 × 10−14 | 5.95 × 10−13 | COL1A1, COL1A2, BMP1, LOX, SERPINH1, P3H1, PLOD2, TNFRSF11B, PLOD1, PPIB, COLGALT1 |
Senescence and autophagy in cancer (WP615) | 1.48 × 10−13 | 6.27 × 10−12 | JUN, SPARC, TGFB1, CXCL8, IGFBP3, SERPINE1, FN1, CXCL1, INHBA, THBS1, COL1A1, IL6, MMP14, COL3A1, CD44 |
Arrhythmogenic right ventricular cardiomyopathy (WP2118) | 9.15 × 10−12 | 3.37 × 10−10 | ITGB1, GJA1, SGCD, ITGB5, CDH2, LAMA2, SGCB, ITGB3, ITGA2, ITGAV, ITGA5, SGCG |
Small cell lung cancer (WP4658) | 1.31 × 10−11 | 4.32 × 10−10 | ITGB1, LAMA2, GADD45B, LAMA1, GADD45A, ITGA2, LAMA3, FN1, LAMC2, LAMC1, COL4A2, COL4A1, ITGAV |
Lung fibrosis (WP3624) | 6.43 × 10−10 | 1.48 × 10−8 | GREM1, IL6, CXCL8, TGFB1, ELN, MMP2, SPP1, PTX3, TIMP1, FGF2 |
Information | Histology | Spirometry | Radiology | |||||||||||
ID | Age | Sex | Smoke | Pack Year | Diagnosis | Gap Index and Stadiation | FEV1 (%) | FVC (%) | Ct Score | Ground Glass | Honey Combing | Consolidations | Cross Linking | Enphysema |
UIP1 | 72 | M | - | - | Possible UIP | II | 90.5 | 77.8 | 30 | No | No | No | Yes | No |
UIP2 | 72 | M | Yes | 37.5 | UIP | I | 110 | 98 | 45 | No | Yes | No | Yes | No |
UIP3 | 78 | F | Yes | 3.75 | Possible UIP | I | 113.9 | 122.30 | 20 | No | Yes | No | Yes | No |
UIP4 | 49 | M | Yes | 15 | UIP | I | 56 | 54 | 50 | Yes | Yes | No | Yes | No |
UIP + LC1 | 75 | M | - | 40 | Lung AdK + UIP | IA2 | 129.30 | 154.70 | 15 | No | No | Yes | Yes | Yes |
UIP + LC2 | 64 | M | Yes | 30 | Lung squamous K + possible UIP | IB | 71 | 68 | 80 | Yes | Yes | No | Yes | Yes |
UIP + LC3 | 76 | M | - | 60 | Lung AdK + possible UIP | IB | 76.7 | 70.4 | 40 | Yes | Yes | Yes | Yes | Yes |
UIP + LC4 | 63 | M | Yes | 34 | Lung squamous K+ possible UIP | IIB | 77.60 | 79.60 | 30 | No | Yes | No | Yes | No |
UIP + LC5 | 74 | M | - | 30 | Lung AdK + UIP | IIB | 92 | 85 | 80 | Yes | Yes | Yes | Yes | No |
UIP + LC6 | 68 | M | - | 5 | Lung AdK+ UIP | IB | 108 | 100 | 20 | Yes | No | Yes | Yes | No |
UIP + LC7 | 79 | M | Yes | 20 | Lung AdK + UIP | IA2 | 129.1 | 119.1 | 15 | Yes | Yes | Yes | Yes | No |
UIP + LC8 | 80 | M | - | - | Lung squamous K+ Possible UIP | IB | 88.4 | 81.1 | - | - | - | - | - | - |
UIP + LC9 | 81 | M | No | - | Lung AdK + possible UIP | IA2 | 100.6 | 89.9 | 5 | Yes | No | Yes | No | No |
UIP + LC10 | 67 | M | - | 80 | Lung AdK + possible UIP | IA3 | 70 | 112 | 20 | No | No | Yes | Yes | Yes |
UIP + LC11 | 78 | M | - | - | Lung squamous K + possible UIP | IIB | 63.10 | 81.20 | 50 | No | Yes | Yes | Yes | Yes |
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De Vitis, C.; D’Ascanio, M.; Sacconi, A.; Pizzirusso, D.; Salvati, V.; Mancini, M.; Scafetta, G.; Cirombella, R.; Ascenzi, F.; Bruschini, S.; et al. B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis. Int. J. Mol. Sci. 2022, 23, 15040. https://doi.org/10.3390/ijms232315040
De Vitis C, D’Ascanio M, Sacconi A, Pizzirusso D, Salvati V, Mancini M, Scafetta G, Cirombella R, Ascenzi F, Bruschini S, et al. B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis. International Journal of Molecular Sciences. 2022; 23(23):15040. https://doi.org/10.3390/ijms232315040
Chicago/Turabian StyleDe Vitis, Claudia, Michela D’Ascanio, Andrea Sacconi, Dario Pizzirusso, Valentina Salvati, Massimiliano Mancini, Giorgia Scafetta, Roberto Cirombella, Francesca Ascenzi, Sara Bruschini, and et al. 2022. "B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis" International Journal of Molecular Sciences 23, no. 23: 15040. https://doi.org/10.3390/ijms232315040