g Immunohistochemical analysis and quantification of TGF- β1, collagen I and ATP5A1 in lung tissue of mouse model ( n = 5). f Correlation analysis between complex V activity and HRCT score of PF patients ( n = 50). e High-resolution computed tomography (HRCT) images at four sections of three patients with different complex V activity levels (0.10, 0.04, and 0.01). d Receiver-operating characteristic (ROC) curve analysis of complex V activity (red)/ combined complex V activity and serum TGF-β levels (green) between PF patients ( n = 50) and HCs ( n = 9). c Correlation analysis of complex V activity and serum TGF-β levels. b Complex V activity of idiopathic PF (IPF) ( n = 41), and connective tissue disease PF (CTD-PF) ( n = 9) and HCs ( n = 9). a Complex V activity of pulmonary fibrosis patients (PF) ( n = 50) and healthy controls (HCs) ( n = 9). Respiratory chain complex V reduction indicates cyto/mito-ribosome imbalance and their different tolerances to free radical bursts in pulmonary fibrosis. 3, S4, and Supplementary Tables 2 and 3). Besides, correlation analyses also reflected that there was the correlation between TGF-β, complex V activity and fibrotic lesions (Fig. Data from a bleomycin (BLM)-induced PF mouse model supported the above results, quantitatively and qualitatively indicating increased expression of TGF-β as well as decreased activity of complex V in both pulmonary tissue and blood samples. These data suggest a potential role for the TGF-β +/complex V− combination as a PF blood biomarker (Fig. In addition, the extent of the fibrotic pattern on high-resolution computed tomography (HRCT) scans was correlated with complex V activity. Further receiver-operating characteristic (ROC) analysis revealed that the PF group and the HC group were well distinguished based on complex V activity levels and especially based on the combination of complex V activity and serum TGF-β levels. Decreased complex V activity was significantly correlated with increased expression of TGF-β.

Decreased RCCs activities, especially complex V, were observed in PF patients. We first examined the TGF-β levels and the enzymatic activity of five RCCs in blood samples of healthy controls (HCs) and patients with the two most common forms of PF, 4 idiopathic PF (IPF) and connective tissue disease PF (CTD-PF).

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