The KLF4-inflammatory pathway is associated with paraquat-induced pulmonary injury and early pro-fibrotic responses

Abstract

Paraquat, a highly toxic herbicide, frequently causes acute poisoning, predominantly inducing pulmonary injury and fibrosis with high mortality, and no specific antidote is available. This study aimed to explore its pathogenesis using a paraquat-induced mouse model. Results showed that paraquat caused dose-dependent body weight changes, pulmonary edema, and pathological damage (alveolar structure destruction, inflammatory cell infiltration), with elevated levels of inflammatory factors (IL-6, TNF-α, IL-1β) in BALF and lung tissues. It also induced pulmonary early pro-fibrotic responses, evidenced by increased collagen deposition and upregulated mesenchymal markers (α-SMA, Vimentin, Collagen I). RNA sequencing revealed KLF4 was significantly downregulated, and differentially expressed genes (DEGs) were enriched in inflammatory pathways. KLF4 negatively correlated with core genes (GSK3B, MLH1, PRKACA, VDAC1, WNT7B) in pathways like Wnt signaling pathway. These findings indicated that paraquat-induced pulmonary injury and early pro-fibrotic responses are associated with KLF4 downregulation and inflammatory pathway activation, identifying KLF4 as a potential therapeutic target for clinical intervention.