Role And Intervention Of Tyrosine Kinase Receptor DDR2 Signal In Murine Pulmonary Fibrosis Model

Pulmonary fibrosis is a highly heterogeneous and lethal pulmonary disease. Pulmonary fibrosis can be caused by virus, radiation therapy, and other factors such as environmental toxins and chemotherapy drugs. The development of pulmonary fibrosis invovles several steps: the irreversible destruction caused by lung structure scarring; disturbed gas exchange leading to respiratory failure and finally the death.DDRs, one highly evolutionarily conserved family of receptor tyrosine kinases, comprising two members DDR1 and DDR2, regulate the signal transductions between the cell and extracellular matrix. Under physiological conditions, DDRs can bind with many different types of collagens, and play a very important role in embryonic development. If DDRs signaling disordered, it will lead to arthritis, cancer, and other diseases such as osteogenesis imperfecta. At the same time, DDRs also extensively involves in cellular fate, including cell migration, survival, proliferation, differentiation, and extracellular matrix remodeling. Previous studies showed that DDR1 knockout mice can effectively protect mice from bleomycin-induced pulmonary fibrosis, and DDR2 is highly expressed in mouse lung tissues, so we speculate that DDR2 signaling pathway plays an important role in the development of pulmonary fibrosis.We mainly studied on following aspects: 1. DDR2 overexpression or DDR2 koncodown in lung tissues and observe its effect on process of pulmonary fibrosis. 2. Immunohistochemistry and immunofluorescence experiments to determine cellular localization of DDR2 in human lung tissues, and further study the regulation its mechanism on cell function. 3. Realtime-PCR and immunofluorescence analysis on whether DDR2 influences the status of experimental pulmonary fibrosis induced angiogenesis. 4. Preliminary study on whether DDR2 participated in tissue repair of pulmonary fibrosis. 5. Research on small molecule inhibitors D856 and Dasatinib in treating pulmonary fibrosis. 6. Preliminary study on the function of TSGA13 gene Conclusion: Collagen receptor DDR2 promote bleomycin-induced pulmonary fibrosis.