CD147 mitochondria translocation induced airway remodeling in asthmatic mouse models by regulating M2 macrophage polarization via ANT1-mediated mitophagy.

Abstract

CD147 has the potential to serve as a specific target with therapeutic characteristics in several respiratory diseases. Studies have demonstrated that CD147 regulates levels of oxidative phosphorylation (OXPHOS) through the process of mitochondrial translocations. However, there is still limited insight in the distinct mechanism of CD147 in asthmatic macrophages. Here, we found that CD147 expression levels increased significantly both in vivo and in vitro. CD147 undergoes mitochondrial translocation in M2 macrophages. Reducing the expression of CD147 resulted in a decline in M2 polarization levels within macrophages, as well as a decrease in the levels of mitochondrial respiratory chain complexes I, II, and IV proteins. This effect may be attained by interacting with adenine nucleotide translocase 1 (ANT1), subsequently impacting the levels of mitophagy. We also discovered that CD147 knockdown significantly reduced airway remodeling and inflammation in addition to lowering the polarization level of M2 in the lung tissues of chronic asthmatic model mice. The findings represent the first evidence of the distinct function of CD147 in the process of airway remodeling in asthma.The interaction between CD147 and ANT1 in M2 macrophages occurs via mitochondrial translocation, resulting in alterations in ANT1 expression levels. This, in turn, triggers the activation of the mitophagy pathway, leading to modifications in OXPHOS levels. Ultimately, these changes contribute to the enhancement of M2 polarization, thereby exacerbating airway remodeling in asthma.