R1R2 peptide ameliorates pulmonary fibrosis in mice through fibrocyte migration and differentiation

Hou-Yu Chiang, Pao-Hsien Chu and Ting-Hein Lee

PLOS ONE, 2017, vol. 12, issue 10, 1-23

Abstract: Circulating fibrocytes play a key role in the pathogenesis of pulmonary fibrosis. Fibrocytes are bone marrow-derived leukocytes, which enter the lungs in response to their chemoattractant CXCL12 and differentiate into fibroblasts or myofibroblasts, leading to excess deposition of the collagen-rich extracellular matrix. Matrix metalloproteinase (MMP)-9 and MMP-2, secreted by fibrocytes, degrade the subendothelial basement membrane and promote fibrocyte influx into the lungs. Here, we demonstrate that R1R2, a novel peptide derived from the bacterial adhesin SFS, attenuates pulmonary fibrosis by preventing the differentiation of fibrocytes into myofibroblasts and by reducing the invasion of fibrocytes through basement membrane-like proteins. Moreover, our findings reveal dual regulation of R1R2 on MMP-9 through reduced enzymatic activity on gelatin and increased cleavage of CXCL12. These data suggest that R1R2 has potent anti-fibrotic effects against pulmonary fibrosis.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0185811

DOI: 10.1371/journal.pone.0185811

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