The role of transforming growth factor beta-receptor III in Kawasaki Disease

Kawasaki Disease (KD) is an acute, self-limited, vasculitis that occurs predominantly in infants and children under the age of 5 (Kawasaki, Kosaki et al. 1974). An intense inflammatory response mediated by cytokine pathways and migration of myofibroblasts created through endothelial/epithelial to mesenchymal transition (EMT) damages the arterial wall. KD is now the most common cause of acquired heart disease in children in developed countries (Taubert, Rowley et al. 1991). Transforming growth factor ß (TGFß) is a multifunctional cytokine that has important roles in cardiovascular remodeling, cellular differentiation, and proliferation, as well as T cell regulation. All of these processes are important in KD. The TGFß superfamily co-receptor III (TGFßRIII) mediates ligand binding in the TGFß pathway, but also has roles in regulation of EMT and cardiovascular development during fetal life. Evaluation of TGFßRIII at the transcript and protein levels showed significantly lower levels of transcript abundance (p<0.05) with simultaneous high protein levels (p<0.05) during the acute phase of KD. All 6 of the IVIG treatment non-responders (100%) showed higher acute sTGFBRIII protein levels compared to the convalescent stage of illness while only 3 of the 13 responders (23%) were above the presumably normal levels. High acute sTGFBRIII protein levels were also detected in Hispanic KD subjects but no difference between ethnicities was present at the transcript level. These results suggest that reduced TGFßRIII transcript levels may contribute to KD pathogenesis, and high sTGFBRIII protein levels may be working to suppress excess inflammation and EMT possibly by decreasing TGFß-2 signalin