Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis
Authors: Guangsuo Wang
Shiyuan Xu
Xin Chen
Yalan Li
Yetong Feng
Hanwei Li
Pengfei Liu
Lei Zhao
Journal: Cellular & Molecular Biology Letters (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Acute lung injury; Ferroptosis; Ferrostatin-1; Lipopolysaccharide.
Affiliations: 1Department of Anesthesiology, The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, The 1st Affiliated Hospitals of Southern University of Science and Technology, Shenzhen, 518020 China., 2Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632 China., 3Health Science Center, School of Basic Medical Sciences, Shenzhen University, Shenzhen, 518037 China., 4Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510280 China., 5Department of Laboratory Medicine, The 2nd Clinical Medicine College (Shenzhen People's Hospital) of Jinan University, The 1st Affiliated Hospitals of Southern University of Science and Technology, Shenzhen, 518020 China., 6Department of Thoracic Surgery, The 2nd Clinical Medicine College (Shenzhen People's Hospital) of Jinan University, The 1st Affiliated Hospitals of Southern University of Science and Technology, Shenzhen, 518020 China., 7Department of Anesthesiology, First Affiliated Hospital of Jinan University, Guangzhou, 510632 China.

Abstract:  Background: Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI. Methods: In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated. Results: The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues. Conclusions: Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients. 

Retracted: No

PubPeer comments:
 Western blot images in this paper appear unusual. *** ![file] *** u201c[T]he raw, uncropped blots for images throughout the paper are shown in Supplementary Fig. 1.u201d Viewed in inverse, they appear as shown below. Could the authors please explain the apparent cropping visible in this Figure? ![file] *** Original ![file] , 
 We appreciate the readeru2019s concern and we are also sorry about the confusing. In our study, all western blot images are taken on a digital imaging system, where a normal white light image of the membrane is captured for the molecular marker, followed by chemiluminescence detection for all protein bands. We think the u201ccroppingu201d phenomenon you noticed is just because of the background of our nitrocellulose membranes or uncleaned substrate buffer on the black exposure board. As it s hard to shown so many images here, we have sent the related white light image to the editor office. You can contact the editor office for the confirmation. In addition, you are also welcome to contact me dirctly. Best regards, Lei Zhao ,