Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Protein kinase C θ deletion ameliorates bleomycin-induced pulmonary fibrosis via the improvement of SIRT1/AMPK signaling on autophagy and senescence

Articles in Press

Document Type : Original Article

Authors
Wei Li 1
Xue Zhao 1
Mengdie Wang 2
Heling Wang 2
Rongyu Li 3
Guoguang Wang 1
1 Department of Pathophysiology, Wannan Medical College, Wuhu, China
2 School of Medical Imaging, Wannan Medical College, Wuhu, China
3 Department of Immunology, Wannan Medical College, Wuhu, China
10.22038/ijbms.2026.93753.20209
Abstract
Objective(s): Protein kinase C theta (PKC θ) is involved in the regulation of various inflammatory diseases, such as allergic asthma and ConA-induced hepatitis. However, its role in pulmonary fibrosis has not been reported. This study aimed to explore the role of PKC θ in bleomycin-induced pulmonary fibrosis and the potential mechanisms involved.
Materials and Methods: WT C57BL/6 and PKC-θ deletion mice were administered a single intratracheal injection of bleomycin at a dosage of 3 mg/kg to prepare an animal model of pulmonary fibrosis. Histopathological changes of lung fibrosis were observed. Blood samples and BALF were collected for biochemical analysis. Protein expression in lung tissues was assessed to investigate a potential mechanism of PKC θ in pulmonary fibrosis.
Results: The results suggested that PKC θ knockout improved pulmonary structure and fibrosis through down-regulating the expression of collagen I and fibronectin, and the TGF-β1 pathway. PKC θ knockout significantly reduced the levels of the inflammatory factors TNF-α, IL-6, and TGF-β in BALF and lung tissues and the NF-κB/IκB-α pathway in the lung. PKC θ knockout also elevated the activities of antioxidant enzymes SOD and CAT, and improved the SIRT1/AMPK-HO-1/Nrf2 pathway. Further, PKC θ knockout ameliorated the expression of the autophagy-related proteins Beclin 1 and p62, and the senescence markers p53 and p21.
Conclusion: These data showed that the improvement in PKC θ knockout in pulmonary fibrosis was associated with enhanced anti-inflammatory and antioxidant effects, activation of autophagy, and reduced senescence effects.
Keywords
Autophagy
Protein kinase C &theta
Pulmonary fibrosis
Senescence
SIRT1/AMPK signaling- pathway
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 17 August 2026