Original title: New ideas for the treatment of pulmonary fibrosis
(Correspondent Wang Yuanyuan Zhang Rui reporter Hao Jingang) Recently, the team of Professor Jiang Xinyi from the School of Pharmacy of Shandong University and Qilu Hospital of Shandong University , Shandong First Medical University, Shandong University of Traditional Chinese Medicine and other units to construct an inhalable mRNA nano-delivery system, which provides a therapeutic benefit for the treatment of pulmonary fibrosis by promoting matrix degradation and alveolar epithelial remodeling in pulmonary fibrosis lesions. new ideas. The research results have been published in Advanced Materials.
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal respiratory disease. The abnormal activation and proliferation of pulmonary fibroblasts in patients with IPF mediates excessive deposition of pulmonary interstitial matrix, excessive scarring of lung tissue, and continuous destruction of alveolar structure, which ultimately leads to impaired pulmonary gas exchange and even loss of pulmonary function. resulting in respiratory failure and death. At present, the clinical treatment of pulmonary fibrosis, in addition to lung transplantation, whether it is drug treatment or non-drug treatment based on pulmonary rehabilitation training, can only slow down the progress of pulmonary fibrosis, but cannot reverse the pulmonary fibrosis lesions. Therefore, it is urgent to Novel therapeutic strategies need to be developed to repair fibrotic lesions and improve lung function in patients.
Increasing matrix metalloproteinase 13 (MMP13) in fibrotic lesions accelerates IPF extracellular matrix (ECM) degradation and restores alveolar space. Jiang Xinyi’s team prepared a nano-delivery system co-loaded with matrix metalloproteinase 13 mRNA (mMMP13) and keratinocyte growth factor (KGF) by double functional modification. The system responds to the release of the outer layer of KGF at the lesion site to promote the proliferation of alveolar epithelial cells; after the mMMP13 recombinant ribosomal protein complex is taken up, the in situ production of MMP13 accelerates the degradation of the extracellular matrix in the alveolar cavity and promotes the repair of fibrotic lesions.
Small animal experiments show that the system can reduce the level of fibrosis in mouse lung tissue, synergistically restore alveolar integrity, and improve the lung function of bleomycin-induced IPF mouse model.
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