Fibrotic extracellular matrix induces release of extracellular vesicles with pro-fibrotic miRNA from fibrocytes

Seidai Sato, Sy Giin Chong, Chandak Upagupta, Toyoshi Yanagihara, Takuya Saito, Chiko Shimbori, Pierre Simon Bellaye, Yasuhiko Nishioka, Martin R.J. Kolb

研究成果: ジャーナルへの寄稿学術誌査読

12 被引用数 (Scopus)

抄録

Extracellular vesicles (EVs) are small lipid vesicles, and EV-coupled microRNAs (miRNAs) are important modulators of biological processes. Fibrocytes are circulating bone marrow-derived cells that migrate into the injured lungs and contribute to fibrogenesis. The question of whether EV-coupled miRNAs derived from fibrocytes are able to regulate pulmonary fibrosis has not been addressed yet. Pulmonary fibrosis was induced in rats by intratracheal administration of an adenoviral gene vector encoding active transforming growth factor-β1 (TGF-β1) or control vector. Primary fibrocytes and fibroblasts were cultured from rat lungs and were sorted by anti-CD45 magnetic beads. Human circulating fibrocytes and fibrocytes in bronchoalveolar lavage fluid (BALF) were isolated by fibronectin-coated dishes. Fibrocytes were cultured on different stiffness plates or decellularised lung scaffolds. We also determined the effects of extracellular matrix (ECM) and recombinant TGF-β1 on the cellular and EV-coupled miRNA expression of fibrocytes. The EVs of fibrocytes derived from fibrotic lungs significantly upregulated the expression ofcol1a1of fibroblasts. Culturing on rigid plates or fibrotic decellularised lung scaffolds increased miR-21-5 p expression compared with soft plates or normal lung scaffolds. Dissolved ECM collected from fibrotic lungs and recombinant TGF-β1 increased miR-21-5 p expression on fibrocytes, and these effects were attenuated on soft plates. Fibrocytes from BALF collected from fibrotic interstitial pneumonia patients showed higher miR-21-5 p expression than those from other patients. Our results indicate that ECM contributes to fibrogenesis through biomechanical and biochemical effects on miRNA expression in fibrocytes.

本文言語英語
ページ(範囲)895-906
ページ数12
ジャーナルThorax
76
9
DOI
出版ステータス出版済み - 9月 1 2021
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 呼吸器内科

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