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Amelioration of paraquat-induced pulmonary fibrosis in mice by regulating miR-140-5p expression with the fibrogenic inhibitor Xuebijing.
Int J Immunopathol Pharmacol. 2020 Jan-Dec; 34:2058738420923911.IJ

Abstract

Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice.

Authors+Show Affiliations

Department of Emergency, First Hospital Affiliated to Kunming Medical University, Kunming, China.Intensive Care Unit, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.Department of Elderly Cardiovascular Diseases, First Hospital Affiliated to Kunming Medical University, Kunming, China.Yunnan Green Field Biological Pharmaceutical Co., Ltd., Kunming, China.Department of Postgraduate, Kunming Medical University, Kunming, China.Department of Postgraduate, Kunming Medical University, Kunming, China.Yunnan Green Field Biological Pharmaceutical Co., Ltd., Kunming, China.Department of Emergency, First Hospital Affiliated to Kunming Medical University, Kunming, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32462952

Citation

Dong, Min-Na, et al. "Amelioration of Paraquat-induced Pulmonary Fibrosis in Mice By Regulating miR-140-5p Expression With the Fibrogenic Inhibitor Xuebijing." International Journal of Immunopathology and Pharmacology, vol. 34, 2020, p. 2058738420923911.
Dong MN, Xiao Y, Li YF, et al. Amelioration of paraquat-induced pulmonary fibrosis in mice by regulating miR-140-5p expression with the fibrogenic inhibitor Xuebijing. Int J Immunopathol Pharmacol. 2020;34:2058738420923911.
Dong, M. N., Xiao, Y., Li, Y. F., Wang, D. M., Qu, Y. P., Fang, T. W., Li, H., & Liu, M. W. (2020). Amelioration of paraquat-induced pulmonary fibrosis in mice by regulating miR-140-5p expression with the fibrogenic inhibitor Xuebijing. International Journal of Immunopathology and Pharmacology, 34, 2058738420923911. https://doi.org/10.1177/2058738420923911
Dong MN, et al. Amelioration of Paraquat-induced Pulmonary Fibrosis in Mice By Regulating miR-140-5p Expression With the Fibrogenic Inhibitor Xuebijing. Int J Immunopathol Pharmacol. 2020 Jan-Dec;34:2058738420923911. PubMed PMID: 32462952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amelioration of paraquat-induced pulmonary fibrosis in mice by regulating miR-140-5p expression with the fibrogenic inhibitor Xuebijing. AU - Dong,Min-Na, AU - Xiao,Yun, AU - Li,Yun-Fei, AU - Wang,Dong-Mei, AU - Qu,Ya-Ping, AU - Fang,Tian-Wen, AU - Li,Hui, AU - Liu,Ming-Wei, PY - 2020/5/29/entrez PY - 2020/5/29/pubmed PY - 2021/3/30/medline KW - Xuebijing KW - matrix metalloproteinase KW - miR-140-5p KW - mice KW - paraquat KW - pulmonary fibrosis KW - transglutaminase-2 SP - 2058738420923911 EP - 2058738420923911 JF - International journal of immunopathology and pharmacology JO - Int J Immunopathol Pharmacol VL - 34 N2 - Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice. SN - 2058-7384 UR - https://www.unboundmedicine.com/medline/citation/32462952/Amelioration_of_paraquat_induced_pulmonary_fibrosis_in_mice_by_regulating_miR_140_5p_expression_with_the_fibrogenic_inhibitor_Xuebijing_ L2 - https://journals.sagepub.com/doi/10.1177/2058738420923911?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -