Regulation of fibronectin levels by agmatine and spermine in mesangial cells under high-glucose conditions

Abstract

Amines such as agmatine, putrescine, spermidine and spermine have been reported to be involved in a variety of physiological and biochemical phenomena. However, it is not known whether they are also involved in the homeostasis of intracellular fibronectin content via upregulation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and transforming growth factor-β1 (TGF-β1). To determine this, we have studied the effect of multiple amines on fibronectin, TGF-β1, ERK, and PKC levels in mesangial cells under high glucose conditions. All the amines tested (at 0.1–1 mM) affected neither the viability of mesangial cells for 42 h nor LDH release into the medium. Agmatine reduced TGF-β1 and ERK levels but not PKC at concentrations of 0.1–1 mM. However, levels of fibronectin, TGF-β1, ERK, and PKC were unaffected by either putrescine or spermidine. A decrease in fibronectin secretion was accompanied by decreases in TGF-β1 and ERK. Such cumulative results lead us to hypothesize that agmatine reduces high glucose-induced fibronectin secretion via several pathways including ERK–TGF-β1–fibronectin and spermine, via a decrease in TGF-β1. Possible roles of enzymes involved in agmatine and polyamine biosynthesis are discussed in relation to secretion of ECM proteins.