論文

査読有り 国際誌
2018年9月13日

Platelets play an essential role in murine lung development through Clec-2/podoplanin interaction.

Blood
  • Nagaharu Tsukiji
  • Osamu Inoue
  • Mitsuru Morimoto
  • Norifumi Tatsumi
  • Hiroaki Nagatomo
  • Koji Ueta
  • Toshiaki Shirai
  • Tomoyuki Sasaki
  • Shimon Otake
  • Shogo Tamura
  • Toshiaki Tachibana
  • Masataka Okabe
  • Masanori Hirashima
  • Yukio Ozaki
  • Katsue Suzuki-Inoue
  • 全て表示

132
11
開始ページ
1167
終了ページ
1179
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1182/blood-2017-12-823369

Platelets participate in not only thrombosis and hemostasis but also other pathophysiological processes, including tumor metastasis and inflammation. However, the putative role of platelets in the development of solid organs has not yet been described. Here, we report that platelets regulate lung development through the interaction between the platelet-activation receptor, C-type lectin-like receptor-2 (Clec-2; encoded by Clec1b), and its ligand, podoplanin, a membrane protein. Clec-2 deletion in mouse platelets led to lung malformation, which caused respiratory failure and neonatal lethality. In these embryos, α-smooth muscle actin-positive alveolar duct myofibroblasts (adMYFs) were almost absent in the primary alveolar septa, which resulted in loss of alveolar elastic fibers and lung malformation. Our data suggest that the lack of adMYFs is caused by abnormal differentiation of lung mesothelial cells (luMCs), the major progenitor of adMYFs. In the developing lung, podoplanin expression is detected in alveolar epithelial cells (AECs), luMCs, and lymphatic endothelial cells (LECs). LEC-specific podoplanin knockout mice showed neonatal lethality and Clec1b-/--like lung developmental abnormalities. Notably, these Clec1b-/--like lung abnormalities were also observed after thrombocytopenia or transforming growth factor-β depletion in fetuses. We propose that the interaction between Clec-2 on platelets and podoplanin on LECs stimulates adMYF differentiation of luMCs through transforming growth factor-β signaling, thus regulating normal lung development.

リンク情報
DOI
https://doi.org/10.1182/blood-2017-12-823369
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29853539
ID情報
  • DOI : 10.1182/blood-2017-12-823369
  • ISSN : 0006-4971
  • PubMed ID : 29853539

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