Vitamin A in serum is a survival factor for fibroblasts

Vitamin A in serum is a survival factor for fibroblasts

^*Department of Pharmacology, Cornell University Medical College, New York, NY 10021; and ^†Immunology Program, Sloan–Kettering Institute, New York, NY 10021

Edited by Ronald M. Evans, Salk Institute for Biological Studies, San Diego, CA, and approved July 7, 1997 (received for review June 2, 1997)

Abstract

Murine 3T3 cells arrest in a quiescent, nondividing state when transferred into medium containing little or no serum. Within the first day after transfer, fibroblasts can be activated to proliferate by platelet-derived growth factor (PDGF) alone; cells starved longer than 1 day, however, are activated only by serum. We demonstrate that endogenous vitamin A (retinol) or retinol supplied by serum prevents cell death and that retinol, in combination with PDGF, can fully replace serum in activating cells starved longer than 1 day. The physiological retinol derivative 14-hydroxy-4,14-retro-retinol, but not retinoic acid, can replace retinol in rescuing or activating 3T3 cells. Anhydroretinol, another physiological retinol metabolite that acts as a competitive antagonist of retinol, blocks cell activation by serum, indicating that retinol is a necessary component of serum. It previously has been proposed that activation of 3T3 cells requires two factors in serum, an activation factor shown to be PDGF and an unidentified survival factor. We report that retinol is the survival factor in serum.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Department of Pharmacology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021. e-mail: jobuck{at}mail.med.cornell.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: PDGF, platelet-derived growth factor; 14-HRR, 14-hydroxy-4,14-retro-retinol; AR, anhydroretinol; EGF, epidermal growth factor.