Identification of soluble transforming growth factor-beta receptor III (sTbeta III) in rat milk

Transforming growth factor-beta (TGF-beta) is present at high concentration s in maternal milk. In milk TGF-beta2 is the predominant isoform. For funct ion TGF-beta2 requires T beta RIII to facilitate efficient binding to the T GF-beta receptor types I and II signalling complex. We have shown that TGF- beta receptor types I (T beta RI), II (T beta RII) and III (T beta RIII) ar e coexpressed in the suckling rat intestine. Immunostaining for T beta RIII was also observed in the intestinal lumen prior to weaning. T beta RIII (o r betaglycan) has been reported in serum, cell culture medium and extracell ular matrix. To determine whether a soluble form of T beta RIII is present in milk, the rat milk aqueous phase was analysed by slot-blot and Western b lot. Soluble T beta RIII was detected in milk throughout lactation. Western blot analysis of rat milk revealed a high molecular weight band of glycosy lated protein of >200 kDa, with a core protein of approximately 110-120 kDa that comigrated with recombinant T beta RIII. Immunoabsorption of soluble T beta RIII (sT beta RIII) from milk resulted in partial depletion of activ e TGF-beta from milk, suggesting that the receptor may interact with ligand in milk. In addition rat pups suckled on mother's milk demonstrated an enh anced labelling of T beta RIII in the gut, as compared with pups fed on a r at milk substitute (RMS). These findings suggest that milk sT beta RIII is functional, and may modulate milk-derived TGF-beta function in the developi ng intestine.