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Regulation of bovine corneal endothelial cell cycle by transforming growth factor-β

  1. Yutaka Motegi1,
  2. Tomohiro Usui1,
  3. Kouichi Ishida1,
  4. Satoshi Kato1,
  5. Hidetoshi Yamashita2,*

Article first published online: 26 SEP 2003

DOI: 10.1034/j.1600-0420.2003.00128.x

Issue

Acta Ophthalmologica Scandinavica

Acta Ophthalmologica Scandinavica

Volume 81, Issue 5, pages 517–525, October 2003

Additional Information

How to Cite

Motegi, Y., Usui, T., Ishida, K., Kato, S. and Yamashita, H. (2003), Regulation of bovine corneal endothelial cell cycle by transforming growth factor-β. Acta Ophthalmologica Scandinavica, 81: 517–525. doi: 10.1034/j.1600-0420.2003.00128.x

Author Information

  1. 1

    Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan

  2. 2

    Department of Ophthalmology, University of Yamagata School of Medicine, Yamagata, Japan

* Hidetoshi Yamashita MD Department of Ophthalmology University of Yamagata Iida-nishi 2-2-2 Yamagata 990–9585 Japan Tel: + 81 236 28 6374 Fax: + 81 236 28 5376 Email: hyama-tky@umin.ac.jp

Publication History

  1. Issue published online: 26 SEP 2003
  2. Article first published online: 26 SEP 2003
  3. Received on November 12th, 2002. Accepted on May 27th, 2003.

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Keywords:

  • bovine corneal endothelial cell;
  • cell cycle;
  • S-phase;
  • signal transduction;
  • TGF-β

Abstract.

Purpose: The transforming growth factor-β (TGF-β) family includes three multifunctional proteins, TGF-β1, TGF-β2 and TGF-β3, expressed in ocular tissue, which are involved in regulating cell differentiation, cell proliferation and other cell functions. TGF-β is present in aqueous humour and regulates corneal endothelial cells. This study explores the mechanism by which TGF-β regulates the cell cycle in cultured corneal endothelial cells.

Methods: The expression of specific receptors for the TGF-β family was investigated at the protein level by affinity cross-linking with radio-iodinated TGF-β1 and immunoprecipitation with specific antibodies to TGF-β receptors. Regulation of entry into the S-phase of the cell cycle was determined by 5-bromo-2′ deoxyuridine (BrdU) incorporation into the cells. The signal transduction pathways were investigated using various blocking agents for protein kinase transducers involved in intracytoplasmic signal transduction.

Results: Cultured bovine corneal endothelial cells were confirmed to express TGF-β type 1 and type 2 receptors and endoglin. In the confluent state, TGF-β1 and TGF-β2 stimulated the cells to progress to the S-phase of the cell cycle through platelet-derived growth factor-B (PDGF-B) chain production and protein kinase C.

Conclusions: TGF-β accelerated cell cycle progression from the G0/G1 phase to the S-phase in cultured corneal endothelial cells, under our experimental conditions, through pathways involving protein kinase C. These pathways are related to the cross-talk between TGF-β and other cytokines. The conditions employed in the present experiments may be useful for investigating the complex cross-talk between various cytokines and growth factors.

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