Small molecule proteomics quantifies differences between normal and fibrotic pulmonary extracellular matrices
| Autor: | Xin-Long Wan, Zhi-Liang Zhou, Peng Wang, Xiao-Ming Zhou, Meng-Ying Xie, Jin Mei, Jie Weng, Hai-Tao Xi, Chan Chen, Zhi-Yi Wang, Zhi-Bin Wang, Pei-Fang Wei |
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| Rok vydání: | 2020 |
| Předmět: |
Paraquat
Male Proteomics Fibrinogen-gamma chain Pulmonary Fibrosis Serum albumin lcsh:Medicine Rats Sprague-Dawley Extracellular matrix 03 medical and health sciences 0302 clinical medicine Pulmonary fibrosis medicine Extracellular Animals Lung biology Chemistry lcsh:R P4HB Original Articles General Medicine medicine.disease Molecular biology Rats medicine.anatomical_structure 030220 oncology & carcinogenesis Small molecular protein biology.protein Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Chinese Medical Journal Chinese Medical Journal, Vol 133, Iss 10, Pp 1192-1202 (2020) |
| ISSN: | 2542-5641 0366-6999 |
| DOI: | 10.1097/cm9.0000000000000754 |
| Popis: | Background:. Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. Methods:. Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. Results:. Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). Conclusions:. Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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