1: Biochem J. 2001 Dec 1;360(Pt 2):507-12. 

Transforming growth factor-beta 1 stimulates vascular smooth muscle cell
L-proline transport by inducing system A amino acid transporter 2 (SAT2) gene
expression.

Ensenat D, Hassan S, Reyna SV, Schafer AI, Durante W.

Houston VA Medical Center, Building 109, Room 130, 2002 Holcombe Blvd, Houston,
TX 77030, USA.

Transforming growth factor-beta1 (TGF-beta 1) is a multifunctional cytokine that
contributes to arterial remodelling by stimulating vascular smooth muscle cell
(SMC) growth and collagen synthesis at sites of vascular injury. Since l-proline
is essential for the synthesis of collagen, we examined whether TGF-beta 1
regulates the transcellular transport of l-proline by vascular SMCs. l-Proline
uptake by vascular SMCs was primarily sodium-dependent, pH-sensitive, blocked by
neutral amino acids and alpha-(methylamino)isobutyric acid, and exhibited
trans-inhibition. Treatment of SMCs with TGF-beta 1 stimulated l-proline
transport in a concentration- and time-dependent manner. The TGF-beta 1-mediated
l-proline uptake was inhibited by cycloheximide or actinomycin D. Kinetic
studies indicated that TGF-beta 1-induced l-proline transport was mediated by an
increase in transport capacity independent of any changes in the affinity for
l-proline. TGF-beta 1 stimulated the expression of system A amino acid
transporter 2 (SAT2) mRNA in a time-dependent fashion that paralleled the
increase in l-proline transport. Reverse transcriptase PCR failed to detect the
presence of SAT1 or amino acid transporter 3 (ATA3) in either untreated or
TGF-beta 1-treated SMCs. These results demonstrate that l-proline transport by
vascular SMCs is mediated predominantly by the SAT and that TGF-beta 1
stimulates SMC l-proline uptake by inducing the expression of the SAT2 gene. The
ability of TGF-beta 1 to induce SAT2 expression may function to provide SMCs
with the necessary levels of l-proline required for collagen synthesis and cell
growth.

PMID: 11716780 [PubMed - indexed for MEDLINE]