UP-REGULATION OF A CHONDROITIN SULFATE EPITOPE DURING REGENERATION OFMOUSE SCIATIC-NERVE - EVIDENCE THAT THE IMMUNOREACTIVE MOLECULES ARE RELATED TO THE CHONDROITIN SULFATE PROTEOGLYCANS DECORIN AND VERSICAN

After transection of adult mouse sciatic nerve, the expression of a ch ondroitin sulphate epitope recognized by the monoclonal antibody 473-H D (mAb 473-HD) was found to be up-regulated. The epitope was localized immunocytochemically mainly in Schwann cell basal laminae and, more w eakly, also in the endoneurium. In cultures of mouse dorsal root gangl ion cells, Schwann cells expressed high levels but fibroblasts only lo w levels of the epitope. To identify the molecule(s) carrying this cho ndroitin sulphate epitope, human sciatic nerves were extracted with ph osphate-buffered saline and shown to contain two chondroitin sulphate proteoglycans of apparent molecular weights of 130 and 900 kDa. The 90 0 kDa and, more weakly, the 130 kDa proteoglycan were reactive with mA b 473-HD, which was found to recognize chondroitin-6-sulphate as epito pe. Following chondroitinase ABC treatment of the 130 kDa proteoglycan , a core protein of similar to 45 kDa was seen and shown to react with polyclonal antibodies against the chondroitin-dermatan sulphate prote oglycan decorin from human fibroblasts. Chondroitinase ABC treatment o f the 900 kDa proteoglycan yielded a core protein with a molecular wei ght of similar to 400 kDa that was recognized by polyclonal antibodies against recombinantly expressed fusion proteins from human versican. After transection of adult mouse sciatic nerves, the distal nerve stum ps showed up-regulation of the chondroitin-6-sulphate epitope of the 9 00 kDa proteoglycan, whereas the core protein of this proteoglycan did not show any detectable change in the level of expression. In contras t, the core protein of the 130 kDa proteoglycan was up-regulated in ex pression. These observations suggest that versican- and decorin-like m olecules may contribute to successful regeneration in the peripheral n ervous system of mammals.