Periostin-An inducer of pro-fibrotic phenotype in monocytes and monocyte-derived macrophages in systemic sclerosis

骨膜素——系统性硬化症中单核细胞和单核细胞衍生的巨噬细胞中促纤维化表型的诱导剂

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作者:Mao Suzuki, Yasushi Ototake, Asami Akita, Miho Asami, Noriko Ikeda, Tomoya Watanabe, Miwa Kanaoka, Yukie Yamaguchi

Abstract

Enhanced circulating blood periostin levels positively correlate with disease severity in patients with systemic sclerosis (SSc). Monocytes/macrophages are predominantly associated with the pathogenesis of SSc, but the effect of periostin on immune cells, particularly monocytes and macrophages, still remains to be elucidated. We examined the effect of periostin on monocytes and monocyte-derived macrophages (MDM) in the pathogenesis of SSc. The modified Rodnan total skin thickness score in patients with dcSSc was positively correlated with the proportion of CD80-CD206+ M2 cells. The proportion of M2 macrophages was significantly reduced in rPn-stimulated MDMs of HCs compared to that of SSc patients. The mRNA expression of pro-fibrotic cytokines, chemokines, and ECM proteins was significantly upregulated in rPn-stimulated monocytes and MDMs as compared to that of control monocytes and MDMs. A similar trend was observed for protein expression in the respective MDMs. In addition, the ratio of migrated cells was significantly higher in rPn-stimulated as compared to control monocytes. These results suggest that periostin promotes inflammation and fibrosis in the pathogenesis of SSc by possible modulation of monocytes/macrophages.

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