Protein Kinase C θ Deletion Ameliorates Bleomycin-Induced Pulmonary Fibrosis Via the Improvement of SIRT1/AMPK Signaling on Autophagy and Senescence

Abstract BACKGROUND PKC θ is involved in the regulation of various inflammatory diseases, such as allergic asthma, and conA-induced hepatitis. However, the effect of PKC θ on pulmonary fibrosis was not reported. This study aimed to explore the role of PKC θ in bleomycin-induced pulmonary fibrosis and its potential mechanisms. METHODS WT C57BL/6 and PKC-θ deletion mice were administrated by a single intratracheal injection of bleomycin at a dosage of 3 mg/kg to prepare animal model of pulmonary fibrosis. Histopathological changes of lung fibrosis were observed. Blood samples and BALF were collected for biochemical analysis. The expression of proteins in lung tissues were determined to assess possible mechanism of PKC θ in pulmonary fibrosis. RESULTS The results suggested that PKC θ knockout improved pulmonary structure and fibrosis through downregulating the expression of collagen I and fibronectin, and the TGF-β1 pathway. PKC θ knockout significantly reduced the levels of TNF-α, IL-6 and TGF-β in BALF and the lung tissues, and the NF-кB/IƘB-ɑ pathway in lung. PKC θ knockout also elevated activities of SOD and CAT, and improved the SIRT1/AMPK-HO-1/Nrf2 pathway. Further, PKC θ knockout ameliorated the expression of autophagy-related protein Beclin 1 and p62, and the markers of senescence p53 and p21 protein. CONCLUSION These data showed that improvement of PKC θ knockout on pulmonary fibrosis was associated with enhancement of anti-inflammation and antioxidation, autophagy activation, and reduction of senescence effects.