The antifibrotic effect of pheretima protein is mediated by the TGF-β1/Smad2/3 pathway and attenuates inflammation in bleomycin-induced idiopathic pulmonary fibrosis.
Journal of ethnopharmacology(2021)
摘要
ETHNOPHARMACOLOGICAL RELEVANCE:Pheretima is a traditional Chinese medicine that could treat various lung diseases such as asthma, pneumonia, and lung cancer effectively; however, limited studies on the use of Pheretima protein in the treatment of lung diseases have been conducted to date.
AIM OF THE STUDY:The aim of this study was to explain the antipulmonary fibrosis mechanism of the Pheretima protein and elucidate its possible cell signaling pathways.
MATERIAL AND METHODS:Fresh pheretima was freeze-dried to obtain the Pheretima protein. Divide C57BL/6 mice into control and bleomycin (BLM)-induced models, pirfenidone, and Pheretima protein-treatment groups. Three weeks later, they were treated with H&E and Masson's trichrome staining to assess lung injury and fibrosis. Pulmonary fibrosis was assessed using immunohistochemistry (IHC), realtime-PCR (RT-PCR), and western blotting. Inflammation was assessed using the alveolar lavage fluid.
RESULTS:Pheretima protein inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition and reduced inflammation. It also reduced the levels of Smad2/3, pSmad2/3, and transforming growth factor-beta 1 (TGF-β1). Thus, our results indicate that Pheretima protein can alleviate BLM-induced pulmonary fibrosis in a mouse model.
CONCLUSION:Pheretima protein inhibits ECM, EMT, and antiinflammatory markers, which in turn ameliorates BLM-induced pulmonary fibrosis. Preliminary mechanistic studies indicated that Pheretima protein can exert its biological activity by downregulating the TGF-β1/Smad2/3 pathway.
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