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Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein.

Abstract：

:Adult rat arterial smooth muscle cells (SMC) in primary culture modulate from contractile to synthetic phenotype. This process includes partial loss of myofilaments and formation of an extensive rough endoplasmic reticulum and a large Golgi complex. It gives the cells the ability to initiate DNA synthesis and actively proliferate when stimulated with serum or isolated growth factors. After a few divisions, growth becomes partly independent of exogenous mitogens and does not cease until multiple cell layers have been formed. Here, it is demonstrated that serum-free conditioned medium from primary cultures of adult rat arterial SMC contains a factor that initiates DNA synthesis in growth-arrested secondary cultures of SMC. The mitogenic activity was neutralized by antibodies to platelet-derived growth factor (PDGF), and no mitogenic activity occurred in conditioned medium from cultures pretreated with actinomycin D, excluding release into the medium of PDGF adsorbed to the plastic vessels during the initial culture in serum-containing medium. Exposure of human fibroblasts to samples of the conditioned medium at 4 degrees C inhibited subsequent binding of 125I-labeled PDGF. It was further shown that the SMC of the primary cultures were able to initiate DNA synthesis in a chemically defined medium lacking PDGF and other growth factors. During the early, most active, and partly autonomous growth phase, the SMC had a low binding capacity for 125I-labeled PDGF and responded but little to stimulation with exogenous PDGF. Later on, with increasing cell density and decreasing growth rate, the ability to bind and respond to exogenous PDGF increased. Taken together, the observations suggest that modulation of SMC from contractile to synthetic phenotype is accompanied by production of a PDGF-like protein and autocrine or possibly by mitogen-independent initiation of DNA synthesis. Functionally, this may be important during wound healing and in the development of atherosclerotic lesions.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Nilsson J,Sjölund M,Palmberg L,Thyberg J,Heldin CH

doi

10.1073/pnas.82.13.4418

subject

Has Abstract

pub_date

1985-07-01 00:00:00

pages

4418-22

issue

eissn

0027-8424

issn

1091-6490

journal_volume

pub_type

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Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein.