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Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats

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Summary

The dynamic variation of renin-angiotensin system (RAS) in silicosis remains unclear. Seventy Wistar rats were divided into 7 groups including control group, silicosis groups (inhaling SiO2 for 2, 4, 8, 16 and 24 weeks, respectively) and Captopril (Cap) group. Rat lung primary fibroblasts were divided into control group, SiO2-stimulated group (0, 0.5, 1, 3, 6, 12, 24 and 48 h) and Cap group. The silicotic nodules were formed and collagens were deposited gradually in silicosis group observed by haematoxylin and eosin (HE) staining and Van Gieson (VG) staining. Cap relieved the lung fibrosis and collagen deposition. Immunohistochemistry indicated the positive expression of α-smooth muscle actin (α-SMA) was increased gradually in silicotic rat lung tissue. Western blotting revealed the expression of collagen type I (Col I) and α-SMA was up-regulated in silicotic rat lung tissue and fibroblasts stimulated by SiO2. Cap decreased the expression of Col I and α-SMA in silicotic rat lung tissue and fibroblasts stimulated by SiO2. Western blotting also demonstrated the expression of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) was increased, and the expression of ACE2 and Mas was decreased gradually in silicotic rat lung tissue and fibroblasts stimulated by SiO2. ELISA showed the serum levels of ACE and angiotensin II (Ang II) were also increased and ACE2 and Ang (1-7) were decreased in the silicosis group. Treatment with Cap decreased the expression levels of ACE, Ang II and AT1, and increased the expression levels of ACE2, Ang (1-7) and Mas. These findings suggested that an imbalance between ACE-Ang II-AT1 axis and ACE2-Ang (1-7)-Mas axis may participate in the development of silicosis.

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Author notes

  1. Both authors contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, North China University of Science and Technology, Tangshan, 063210, China

    Bo-nan Zhang

  2. Hebei Key Laboratory for Organ Fibrosis, Medical Research Center, North China University of Science and Technology, Tangshan, 063210, China

    Bo-nan Zhang, Xin Zhang, Hong Xu, Gui-zhen Zhang, Hui Zhang & Fang Yang

  3. Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Clinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, China

    Bo-nan Zhang

  4. Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, China

    Xue-min Gao

Authors
  1. Bo-nan Zhang
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  2. Xin Zhang
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  3. Hong Xu
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  4. Xue-min Gao
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  5. Gui-zhen Zhang
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  6. Hui Zhang
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  7. Fang Yang
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Corresponding author

Correspondence to Fang Yang.

Additional information

This study was supported by grants from the National Natural Science Foundation of China (No. 81472953), Natural Science Foundation of Hebei Province (No. H2016209170), Graduate Student Innovation Fund of Hebei Province (No. 2016196), Graduate Student Innovation Fund of North China University of Science and Technology (No. 2016B10) and Undergraduate Innovative Project of North China University of Science and Technology (No. X2017354).

Conflict of Interest Statement

We declare that there are no relevant financial or non-financial conflicts of interest in the study.

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Zhang, Bn., Zhang, X., Xu, H. et al. Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats. CURR MED SCI 39, 551–559 (2019). https://doi.org/10.1007/s11596-019-2073-8

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  • DOI: https://doi.org/10.1007/s11596-019-2073-8

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