Specific stimulation of basal lamina heparan sulfate proteoglycan in mouse uterine epithelium by Matrigel and by transforming growth factor-beta 1.

The basal lamina of differentiated epithelium normally turns over only slowly unless stimulated by tissue repair and growth. We show here that one mechanism of this stimulation, as modeled by basal lamina proteoglycan synthesis, may be the release of basal lamina-bound transforming growth factor (TGF-beta). A large heparan sulfate proteoglycan (HSPG, 0.2 Kav on Sepharose CL-4B) that was extractable from mouse uterine epithelium with 4 M guanidine-HCl or 1 M KCl was recognized by a specific monoclonal antibody to the basal lamina HSPG, perlecan. This HSPG was metabolically inactive with respect to [35S]-sulfate labeling in pieces of whole uterus during 4 h of culture, but it was labeled in isolated cells under the same conditions, provided that the cells had been cultured at least 6 to 12 h before labeling. The rate of labeling was then constant during at least 4 days in culture in serum-containing medium. Cultures on Matrigel showed an enhanced [35S]-sulfate labeling specifically in the 0.2 Kav HSPG fraction. Partial stimulation was obtained with a serum-free medium extract of Matrigel, which fractionated on Sephadex G-50 in two components; a major one > 30 kDa and the other at about 15 to 25 kDa. The specific stimulation was mimicked by the addition of 10 ng/ml of TGF-beta 1, but there was no specific stimulation by basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulinlike growth factor-1 (IGF-1), or interleukin-1 (IL-1).(ABSTRACT TRUNCATED AT 250 WORDS)