1: Circulation. 2001 Feb 27;103(8):1121-7. 

Transforming growth factor-beta(1) stimulates L-arginine transport and
metabolism in vascular smooth muscle cells: role in polyamine and collagen
synthesis.

Durante W, Liao L, Reyna SV, Peyton KJ, Schafer AI.

Houston VA Medical Center and the Department of Medicine, Baylor College of
Medicine, Houston, TX 77030, USA. wdurante@bcm.tmc.edu

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) contributes to
arterial remodeling by stimulating vascular smooth muscle cell (VSMC) growth and
collagen synthesis at sites of vascular injury. Because L-arginine is
metabolized to growth-stimulatory polyamines and to the essential collagen
precursor L-proline, we examined whether TGF-beta(1) regulates the transcellular
transport and metabolism of L-arginine by VSMCs. METHODS AND RESULTS:
TGF-beta(1) increased L-arginine uptake, and this was associated with a
selective increase in cationic amino acid transporter-1 (CAT-1) mRNA. In
addition, TGF-beta(1) stimulated L-arginine metabolism by inducing arginase I
mRNA and arginase activity. TGF-beta(1) also stimulated L-ornithine catabolism
by elevating ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT)
activity. TGF-beta(1) markedly increased the capacity of VSMCs to generate the
polyamine putrescine and L-proline from extracellular L-arginine. The
TGF-beta(1)-mediated increase in putrescine and L-proline production was
reversed by methyl-L-arginine, a competitive inhibitor of cationic amino acid
transport, or by hydroxy-L-arginine, an arginase inhibitor. Furthermore, the
formation of putrescine was inhibited by the ODC inhibitor
alpha-difluoromethylornithine, and L-proline generation was blocked by the OAT
inhibitor L-canaline. L-Canaline also inhibited TGF-beta(1)-stimulated type I
collagen synthesis. CONCLUSIONS: These results demonstrate that TGF-beta(1)
stimulates polyamine and L-proline synthesis by inducing the genes that regulate
the transport and metabolism of L-arginine. In addition, they show that
TGF-beta(1)-stimulated collagen production is dependent on L-proline formation.
The ability of TGF-beta(1) to upregulate L-arginine transport and direct its
metabolism to polyamines and L-proline may contribute to arterial remodeling at
sites of vascular damage.

PMID: 11222476 [PubMed - indexed for MEDLINE]