Tamm‐Horsfall protein binds TGF‐ß2

Abstract

The purpose of this study was to determine if Tamm‐Horsfall protein (THP), an abundant protein in urine, interacts with transforming growth factor‐beta (TGF‐ß). Binding between THP and TGF‐ß2 (Genzyme, Cambridge, MA) was evaluated by two techniques, an ELISA and a resonant mirror biosensor (IAsys, NeoSensors Ltd., Durham, UK). The ELISA experiments revealed binding between THP and TGF‐ß2 (KD≈3 × 10−6 M) that was inhibited by soluble THP in a dose dependent manner. In the IAsys experiments, TGF‐ß2 bound to immobilized THP with a KD≈1 × 10−7 M. This binding was specifically inhibited by soluble THP. The above experiments were performed with THP from one female volunteer. A single male THP sample bound TGF‐ß2 1000‐fold less strongly, even though both THP samples bound C1q (another THP ligand) similarly. In light of the significant role of TGF‐ß in the progression of renal fibrosis, the interaction between this profibrogenic factor and an abundant urinary protein, THP, warrants further investigation, including evaluation of biochemical differences between THP samples influencing TGF‐ß2 binding activities. (TGF‐β2 was a generous gift from Genzyme Corp., Cambridge, MA.)