PKC/MAPK signaling suppression by retinal pericyte conditioned medium prevents retinal endothelial cell proliferation

Tetsu Kondo, Ken Ichi Hosoya, Satoko Hori, Masatoshi Tomi, Sumio Ohtsuki, Tetsuya Terasaki

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Little is known about the regulation mechanism of endothelial cell proliferation by retinal pericytes. The purpose of this study was to elucidate the suppression mechanism of retinal capillary endothelial cell growth by soluble factors derived from retinal pericytes. Conditioned medium of retinal pericytes (rPCT1-CM) suppressed ischemia-induced retinal neovascularization. The growth and DNA synthesis of TR-iBRB2 cells, a conditionally immortalized rat retinal capillary endothelial cell line, were suppressed in a concentration-dependent manner by concentrated rPCT1-CM. The number of human cultured endothelial cells was also reduced by rPCT1-CM. These results provide the first evidence that CM from the cultivation of pericytes alone can inhibit retinal neovascularization in vivo and in vitro. Although the growth reduction of TR-iBRB2 cells was only partly reversed by treatment of rPCT1-CM with antibodies to transforming growth factor-β1, it was completely lost by heat-treatment of rPCT1-CM, suggesting that anti-angiogenic factors are soluble proteins. The levels of expression of G1/S-phase-related proteins, such as cyclin D1, cyclin-dependent kinase (cdk)4, cdk6, and proliferating cell nuclear antigen, were reduced and a cdk inhibitor, p21Cip1, was induced in rPCT1-CM-treated TR-iBRB2 cells. Moreover, phosphorylated p44/42 mitogen-activated protein kinase (p44/42 MAPK) in TR-iBRB2 cells was reduced by rPCT1-CM treatment and phosphorylated protein kinase C (PKC)α/βII, which is upstream of p44/42 MAPK, was also suppressed. In conclusion, CM from retinal pericytes suppresses PKC-p44/42 MAPK signaling, inhibits endothelial cell growth, and prevents retinal neovascularization. Anti-angiogenic factors derived from retinal pericytes are likely to play a critical role in the regulation of retinal endothelial cell growth.

Original languageEnglish
Pages (from-to)378-386
Number of pages9
JournalJournal of Cellular Physiology
Volume203
Issue number2
DOIs
Publication statusPublished - 2005 May
Externally publishedYes

Fingerprint

Pericytes
Endothelial cells
Cell proliferation
Conditioned Culture Medium
Protein Kinase C
Endothelial Cells
Cell Proliferation
Retinal Neovascularization
Cell growth
Mitogen-Activated Protein Kinases
Angiogenesis Inducing Agents
Growth
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases
Cyclin D1
Proliferating Cell Nuclear Antigen
G1 Phase
Transforming Growth Factors
S Phase
Rats

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

PKC/MAPK signaling suppression by retinal pericyte conditioned medium prevents retinal endothelial cell proliferation. / Kondo, Tetsu; Hosoya, Ken Ichi; Hori, Satoko; Tomi, Masatoshi; Ohtsuki, Sumio; Terasaki, Tetsuya.

In: Journal of Cellular Physiology, Vol. 203, No. 2, 05.2005, p. 378-386.

Research output: Contribution to journalArticle

Kondo, Tetsu ; Hosoya, Ken Ichi ; Hori, Satoko ; Tomi, Masatoshi ; Ohtsuki, Sumio ; Terasaki, Tetsuya. / PKC/MAPK signaling suppression by retinal pericyte conditioned medium prevents retinal endothelial cell proliferation. In: Journal of Cellular Physiology. 2005 ; Vol. 203, No. 2. pp. 378-386.
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