Differentiation-inducing factor-1, a morphogen of Dictyostelium, induces G1 arrest and differentiation of vascular smooth muscle cells

Yoshikazu Miwa, Toshiyuki Sasaguri, Chiya Kosaka, Yoji Taba, Akio Ishida, Takeo Abumiya, Yuzuru Kubohara

Research output: Contribution to journalArticle

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Abstract

Differentiation-inducing factor-1 (DIF-1) is a morphogen that induces differentiation of Dictyostelium. Recently, DIF-1 has been shown to inhibit proliferation and induce differentiation in tumor cells, although the underlying mechanisms remain unknown. In this study, we examined the effects of DIF-1 on the proliferation and differentiation of vascular smooth muscle cells, to explore novel therapeutic strategies for atherosclerosis. DIF-1 nearly completely inhibited DNA synthesis and cell division in mitogen- stimulated cells. DIF-1 inhibited the phosphorylation of the retinoblastoma protein and the activities of cyclin-dependent kinase (Cdk) 4, Cdk6, and Cdk2, which phosphorylate the retinoblastoma protein. DIF-1 strongly suppressed the expression of cyclins D1, D2, and D3, as well as those of cyclins E and A, which normally began after that of the D-type cyclins. The mRNAs for the smooth muscle myosin heavy chains SM1 and SM2 were expressed in quiescent cells in primary culture, and these expression levels decreased after mitogenic stimulation. In the presence of DIF-1, the rate of the reduction was significantly decelerated. Moreover, the addition of DIF-1 to dedifferentiated cells induced the expressions of SM1 and SM2, accompanied by a reduction in the level of SMemb, a nonmuscle-type myosin heavy chain. Therefore, DIF-1 seemed to interrupt a very early stage of G1 probably by suppressing the expressions of the D-type cyclins. Furthermore, this compound may prevent phenotypic modulation and induce differentiation of vascular smooth muscle cells.

Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalCirculation research
Volume86
Issue number1
DOIs
Publication statusPublished - Jan 7 2000

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Dictyostelium
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cyclin D
Retinoblastoma Protein
Myosin Heavy Chains
Cyclin D3
Cyclin D2
Cyclin-Dependent Kinase 4
Smooth Muscle Myosins
1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone
Cyclin A
Cyclin E
Primary Cell Culture
Cyclin D1
Mitogens
Cell Division
Atherosclerosis
Phosphorylation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Differentiation-inducing factor-1, a morphogen of Dictyostelium, induces G1 arrest and differentiation of vascular smooth muscle cells. / Miwa, Yoshikazu; Sasaguri, Toshiyuki; Kosaka, Chiya; Taba, Yoji; Ishida, Akio; Abumiya, Takeo; Kubohara, Yuzuru.

In: Circulation research, Vol. 86, No. 1, 07.01.2000, p. 68-75.

Research output: Contribution to journalArticle

Miwa, Yoshikazu ; Sasaguri, Toshiyuki ; Kosaka, Chiya ; Taba, Yoji ; Ishida, Akio ; Abumiya, Takeo ; Kubohara, Yuzuru. / Differentiation-inducing factor-1, a morphogen of Dictyostelium, induces G1 arrest and differentiation of vascular smooth muscle cells. In: Circulation research. 2000 ; Vol. 86, No. 1. pp. 68-75.
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