Rapamycin attenuates the paraquat‐induced pulmonary fibrosis through activating Nrf2 pathway

Abstract

Oxidative stress is a key regulator of idiopathic pulmonary fibrosis. Paraquat (PQ)‐induced pulmonary fibrosis seriously endangers people's health. Rapamycin has been reported to alleviate PQ‐induced pulmonary fibrosis, but its underlying mechanism is unclear. The nuclear factor E2‐related factor 2 (Nrf2) plays an important regulatory role in the antioxidant therapy of PQ‐induced pulmonary fibrosis. In this study, we tried to confirm that rapamycin attenuates PQ‐induced pulmonary fibrosis by regulating Nrf2 pathway. In vivo, we proved that rapamycin could inhibit the degree of PQ‐induced oxidant stress as well as enhanced the expression of Nrf2. In vitro, rapamycin decreased the upregulated effects of cell death and apoptosis, fibrosis‐related factors expression and fibroblast‐to‐myofibroblast transformation by PQ treatment. In vivo, rapamycin treatment reduced fibrosis degree and the expression of fibrosis‐related factors in lung tissues of rat treated PQ. Furthermore, we also found that Nrf2 knockdown reduced the inhibitory effect of rapamycin on PQ‐induced pulmonary fibrosis, as well as decreased Nrf2 transfer from the cytoplasm into the nucleus. Our findings demonstrated that the protective effect of rapamycin is associated with the activation of the Nrf2 pathway in pulmonary fibrosis induced by PQ poisoning.

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

“…Immunohistochemical staining was performed to observe the histomorphology and examine the expression of E-cadherin (1:1000, ab1416, Abcam, UK) and α-SMA (1:2000, ab32575, Abcam, UK) according to the previous studies [39]. Hematoxylin-Eosin (H&E) staining and Masson staining were performed to observe the morphological changes of lung tissues according to our previous studies [57].…”

A novel simple risk model to predict the prognosis of patients with paraquat poisoning

“…PQ exposure is a major cause of fatal poisoning in most Asian nations. PQ can cause severe multiple organ damage, such as lungs and gastrointestinal tract, which are the main causes of death after PQ poisoning [21][22][23] . Although therapeutic strategies for the management of acute PQ poisoning have been extensively investigated, PQ poisoning remains poor 24,25 .…”

Curcumin protects murine lung mesenchymal stem cells from H2O2 by modulating the Akt/Nrf2/HO-1 pathway

“…Akt plays an important role in cell survival and apoptosis and participates in the activation and nuclear translocation of Nrf2 through phosphorylation. 30 The Akt/Nrf2/HO-1 pathway is closely related to oxidative stress and apoptosis. Several studies have described agents that alleviate cellular oxidative damage through this pathway.…”