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

Area of Science:

• Pulmonary Medicine
• Toxicology
• Molecular Biology

Background:

• Idiopathic pulmonary fibrosis is regulated by oxidative stress.
• Paraquat (PQ) exposure causes severe pulmonary fibrosis, posing a health risk.
• Rapamycin shows potential in mitigating PQ-induced fibrosis, but its mechanism remains elusive.

Purpose of the Study:

• To investigate whether rapamycin attenuates PQ-induced pulmonary fibrosis by regulating the Nrf2 pathway.
• To elucidate the molecular mechanisms underlying rapamycin's protective effects against PQ-induced lung injury.

Main Methods:

• In vivo studies using a rat model of PQ-induced pulmonary fibrosis.
• In vitro experiments assessing cell death, apoptosis, and fibrosis-related factor expression.
• Analysis of Nrf2 pathway activation, including its translocation to the nucleus.
• Nrf2 knockdown experiments to confirm its role in rapamycin's efficacy.

Main Results:

• Rapamycin significantly inhibited PQ-induced oxidative stress and enhanced Nrf2 expression in vivo.
• In vitro, rapamycin counteracted PQ-induced cell death, apoptosis, and fibroblast activation.
• Rapamycin treatment reduced lung tissue fibrosis and fibrosis-related factor expression in PQ-exposed rats.
• Nrf2 knockdown diminished rapamycin's protective effects, indicating Nrf2 pathway involvement.

Conclusions:

• Rapamycin effectively attenuates paraquat-induced pulmonary fibrosis.
• The protective effect of rapamycin is mediated through the activation of the nuclear factor E2-related factor 2 (Nrf2) pathway.
• Targeting the Nrf2 pathway represents a promising therapeutic strategy for pulmonary fibrosis.