BoxA-calcium phosphate nanoparticle as the treatment for pulmonary fibrosis in rat model

Pulmonary fibrosis is a suffocating disease. The patients whose diagnosed by it mostly have periodic difficulty breathing or long-term experience of shortness of breath on daily basis which resulted in decreased in quality of life. The median survival rate is 3 years after diagnosis in the severe cases. One of the most common severe forms of pulmonary disease is the Idiopathic Pulmonary Fibrosis (IPF). There is currently no consensus on the precise mechanism of the pulmonary fibrosis. The cause of the pulmonary fibrosis can be varying from simple lung infection or mechanical injury to autoimmune disease or radiation exposure. All the causes share the common route which is chronic inflammation and cellular senescence. The chronic inflammation led to DNA instability and transcriptional error result in senescent. The progression of the senescent of the cell led to dysregulation of cell’s function and result in excessive production of fibrous tissue, growth factor, inflammatory cytokine and reduction of fibrolysis process and normal structural protein production ultimately led to the development of pulmonary fibrosis. High Mobility Group Box 1 (HMGB1) protein play an important role in the DNA stability, and inflammatory response of many chronic inflammatory diseases. When HMGB1 is in nucleus, it organizes DNA structure, relieve DNA tension, stabilize DNA, and regulate DNA transcription. When HMGB1 is migrate into cytoplasm or secrete out of cell it loses the intranuclear DNA protective function and also binds to the receptor and activate the pro-inflammatory response which worsen the fibrosis condition. Box A portion of the HMGB1 protein play the main role of DNA stabilization, reduce transcriptional error, and extranuclear controlled inflammation. Therefore, we hypothesized that by administer the BoxA-protein producing plasmid -Calcium-phosphate conjugated nanoparticle, we might be able to stop the fibrogenesis of the lung tissue, normalized the fibrolysis process and increase structural protein production such as surfactant protein within the rat model which have develop pulmonary fibrosis induced by Bleomycin. This could lead to the potential treatment for IPF which doesn’t have the effective treatment yet.