PGAM5 Modulates Macrophage Polarization, Aggravating Inflammation in COPD via the NF-κB Pathway

Yu Zheng,1,2,* Yujie Wang,1,* Jia Li,2 Shaomao Zheng,1 Lipeng Zhang,2 Qiaoyu Li,2 Fayu Ling,3 Qiuli Nie,2 Qiong Feng,1 Jing Wang,1,4 Chengji Jin1 1Department of Respiratory Medicine, The second Affiliated Hospital, Hainan Medical University, Haikou, 570100, People’s Republic of China; 2The Second School of Clinical Medicine, Hainan Medical University, Haikou, 570100, People’s Republic of China; 3Department of Thoracic Surgery, The second Affiliated Hospital, Hainan Medical University, Haikou, 570100, People’s Republic of China; 4NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, 571199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wang, Email [email protected]; Chengji Jin, Email [email protected]: Chronic obstructive pulmonary disease (COPD) has emerged as a very consequential issue threatening human life and health; therefore, research on its pathogenesis is urgently needed. A prior investigation discovered a significant elevation in the phosphoglycerate mutase 5 (PGAM5) expression in the lung tissue of COPD smoking patients. This rise in expression is closely associated with COPD severity. Nevertheless, the precise molecular processes by which PGAM5 influences the COPD initiation and advancement remain unknown.Materials and Methods: A COPD model was created using murine alveolar macrophages (MH-S). Flow cytometry, enzyme-linked immunosorbent assay, Western blotting, and other methods were used to detect macrophage polarization, inflammatory factor secretion levels, and changes in PGAM5 and the nuclear factor-κB (NF-κB) pathway.Results: PGAM5 stimulated macrophage M1 polarization and secretion of the proinflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). PGAM5 bound and activated apoptotic signaling-regulated kinase 1 (ASK1), further activating the NF-κB pathway. These implications were reversed when PGAM5 expression was silenced.Conclusion: PGAM5 can cause an increase in p-ASK1T838, trigger the NF-κB pathway activation, and stimulate the M1 macrophage polarization and production of proinflammatory factors. This finding has significant implications for preventing and treating COPD.Keywords: COPD, phosphoglycerate mutase 5, macrophage polarization, NF-κB pathway, apoptosis signal-regulating kinase 1