A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice.
Anghesom GhebremedhinAhmad Bin SalamBenjamin Adu-AddaiSteve NoonanRichard StrattonMd Shakir Uddin AhmedChandra KhantwalGeorge R MartinHuixian LinChris AndrewsBalasubramanyanam KaranamUdo RudloffHenry LopezJesse M JaynesClayton C YatesPublished in: Cells (2023)
Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-β1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-β1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis.
Keyphrases
- long non coding rna
- pulmonary fibrosis
- poor prognosis
- idiopathic pulmonary fibrosis
- early stage
- high glucose
- interstitial lung disease
- nk cells
- rheumatoid arthritis
- drug induced
- liver fibrosis
- signaling pathway
- cancer therapy
- type diabetes
- computed tomography
- mass spectrometry
- radiation therapy
- adipose tissue
- transforming growth factor
- blood brain barrier
- oxidative stress
- drug delivery
- systemic sclerosis
- endothelial cells
- sentinel lymph node
- wild type
- stress induced
- lymph node
- magnetic resonance imaging
- skeletal muscle
- rectal cancer
- dendritic cells