c-Met expression induction in immune cells modulates pulmonary fibrosis progression

Pulmonary fibrosis (PF) is the end pathologic stage of several interstitial lung diseases associated with high morbidity and mortality rates. However, the treatments used in clinical practice are only capable to slow the disease progression rather than stop it. Evidences have shown critical roles of chronic inflammation in the progression of PF-associated diseases. However, the drivers of these effects are still unknown. Therefore, new insights about the immune regulation of PF are fundamental to develop more efficient therapeutic approaches. Growing evidences have shown the role of hepatocyte growth factor (HGF) and its receptor (c-Met) in modulation of immune cell’s migratory capacity and functions, namely its upon inflammatory stimuli and required for extravasation of neutrophil to inflamed tumours. Nevertheless, the effects of this signalling in immune cells in the context of PF-associated lung diseases remains unexplored. Therefore, we used a bleomycin‑induced PF model to understand the contribution of c‑Met‑expressing immune cells to PF progression. Interestingly, our data demonstrate that inflammatory cells and c-Met expression induction was specially observed on T cells and interstitial macrophages. Furthermore, in a cell‑specific transgenic mouse, in which c-Met was deleted in hematopoietic and endothelial cells, c-Met expression correlated with an increment in inflammatory infiltration, namely neutrophils and interstitial macrophages, and reduction of proinflammatory cytokines, along with higher tissue destruction and collagen deposition. Thus, our findings point out HGF/c‑Met signalling as a critical player in the pathogenesis of PF, probably through immune cells.