The physiologic and pathologic roles of Tamm-Horsfall glycoprotein in urinary system

Tamm-Horsfall glycoprotein (THG), a unique renal glycoprotein, is synthesized exclusively by the epithelial cells of the thick ascending loop of Henle and early segment of distal convoluted tubules. The protein is the primary constituent of urinary hyaline cast. The aggregation and gel formation of THG in response to increasing concentrations of electrolytes and low pH within physiologic ranges may affect the permeability of water in this segment. The dual effect of THG on mononuclear cells renders the molecule to become a potent immunomodulator. The cytokine-binding activity of THG lets the kidney an important tissue for cytokine catabolism. The aggregation characteristics of THG also plays a role in pathologic states and leads to the persistence of interstitial deposits in several tubulointerstitial diseases. The induction of immune responses to this protein, including urinary tract infection, reflux nephropathy chronic active hepatic damage, elicites immune complex tubulointerstitial nephritis. It is expected that the detection of THG or its antibodies may aid in the diagnosis of renal tubular disorders.