Identification of soluble transforming growth factor-β receptor III (sTβIII) in rat milk

Transforming growth factor-β (TGF-β) is present at high concentrations in maternal milk. In milk TGF-β2 is the predominant isoform. For function TGF-β2 requires TβRIII to facilitate efficient binding to the TGF-β receptor types I and II signalling complex. We have shown that TGF-β receptor types I (TβRI), II (TβRII) and III (TβRIII) are coexpressed in the suckling rat intestine. Immunostaining for TβRIII was also observed in the intestinal lumen prior to weaning. TβRIII (or betaglycan) has been reported in serum, cell culture medium and extracellular matrix. To determine whether a soluble form of TβRIII is present in milk, the rat milk aqueous phase was analysed by slot-blot and Western blot. Soluble TβRIII was detected in milk throughout lactation. Western blot analysis of rat milk revealed a high molecular weight band of glycosylated protein of >200 kDa, with a core protein of approximately 110-120 kDa that comigrated with recombinant TβRIII. Immunoabsorption of soluble TβRIII (sTβRIII) from milk resulted in partial depletion of active TGF-β from milk, suggesting that the receptor may interact with ligand in milk. In addition rat pups suckled on mother's milk demonstrated an enhanced labelling of TβRIII in the gut, as compared with pups fed on a rat milk substitute (RMS). These findings suggest that milk sTβRIII is functional, and may modulate milk-derived TGF-β function in the developing intestine.