FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-Kappa B signaling

doi:10.21037/atm-22-4389

科研成果详情

题名	FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-Kappa B signaling
作者	Wang, Qiang 1,2; Shi, Qiangqiang 2,3; Liu, Li 2; Qian, Yao2; Dong, Nian 2
发表日期	2022-10-25
发表期刊	ANNALS OF TRANSLATIONAL MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Particulate matter (PM) fibroblast growth factor 10 (FGF10) oxidative stress nuclear factor-KB (NF-KB) nuclear factor erythroid 2 related factor 2 (Nrf2)
其他关键词	OXIDATIVE STRESS ; GROWTH-FACTOR ; INFLAMMATION ; INHIBITION ; ACTIVATION
摘要	Background: Particulate matter (PM), a well-known environmental pollutant, is an independent risk factor associated with the morbidity of various respiratory diseases. Oxidative stress is an important pathophysiological mechanism related to PM exposure, which mediates redox-sensitive inflammatory signaling, leading to lung injury. Fibroblast growth factor 10 (FGF10), a paracrine fibroblast growth factor that mediates mesenchymal to epithelial signaling, participates in epithelial repair during lung injury. However, whether FGF10-mediated repair in PM-induced lung injury is related to the regulation of oxidative stress remains to be elucidated. Methods: In vivo, the C57BL/6 mice were randomly divided, with intratracheal instillation of 5 mg/kg FGF10 1 h before 4 mg/kg PM for 2 consecutive days. In vitro, the BEAS-2B cells were pretreated with 10 ng/mL FGF10 before exposed to 200 mu g/mL PM. Besides, the specific Nrf2 inhibitor ML385 was adopted in vitro. The harvested lung tissues were pathologic grading scored. The state of oxidative stress was assessed with dihydroethidium (DHE) staining, malondialdehyde (MDA) activity, hydrogen peroxide (H2O2) assays and reactive oxygen species (ROS). The contents of IL-6 and IL-8 in bronchoalveolar lavage (BAL) as well as culture supernatant were quantified by ELISA. The protein levels of nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-KB (NF-KB) signaling from lung tissue as well as cell lysate were determined by Western blot. Results: In this study, recombinant FGF10 administration relieved the degree of lung injury, which is characterized by bronchitis, in a mouse model of PM exposure. In addition, reduced ROS levels, which are indicative of restrained oxidative stress, were also observed. Moreover, two redox-sensitive signaling pathways, Nrf2 and NF-KB, were found to be differentially regulated by FGF10. Using a cellular model of PM exposure, we found that the anti-inflammatory effect of FGF10 on NF-KB signaling was mediated through the regulation of oxidative stress. The anti-oxidative effect relied on the stimulation of Nrf2 signaling. Blockade of Nrf2 signaling with ML385 significantly compromised the anti-inflammatory effect of FGF10. Conclusions: These results underscore that the protective anti-oxidative effects of FGF10 in lung injury are mediated by the stimulation of Nrf2 signaling and inhibition of the NF-KB pathway.
资助项目	Zhejiang Provincial Science Technology Department Foundation [2020RC080, 2022RC203]; Wenzhou Technology Foundation [Y20220035]
出版者	AME PUBLISHING COMPANY
ISSN	2305-5839
EISSN	2305-5847
卷号	10 期号:22
DOI	10.21037/atm-22-4389
页数	15
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS记录号	WOS:000883018400001
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	36544647
通讯作者地址	[Dong, Nian]Wenzhou Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Key Lab Intervent Pulmonol Zhejiang Prov, Wenzhou, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/174706
专题	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科其他_附属东阳医院（东阳市人民医院）
通讯作者	Dong, Nian
作者单位	1.Zhejiang Univ, Jinhua Municipal Cent Hosp, Dept Resp Med, Jinhua Hosp, Jinhua, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Key Lab Intervent Pulmonol Zhejiang Prov, Wenzhou, Peoples R China; 3.Wenzhou Med Univ, Affiliated Dongyang Hosp, Dept Resp Med, Jinhua, Peoples R China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
推荐引用方式 GB/T 7714	Wang, Qiang,Shi, Qiangqiang,Liu, Li,et al. FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-Kappa B signaling[J]. ANNALS OF TRANSLATIONAL MEDICINE,2022,10(22).
APA	Wang, Qiang, Shi, Qiangqiang, Liu, Li, Qian, Yao, & Dong, Nian. (2022). FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-Kappa B signaling. ANNALS OF TRANSLATIONAL MEDICINE, 10(22).
MLA	Wang, Qiang,et al."FGF10 mediates protective anti-oxidative effects in particulate matter-induced lung injury through Nrf2 and NF-Kappa B signaling".ANNALS OF TRANSLATIONAL MEDICINE 10.22(2022).