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Reciprocal actions of Wnt9A and BMP4 on chondroitin‐4‐sulfotransferase (CHST11) expression in relation to arylsulfatase B activity (1005.2)
Author(s) -
Bhattacharyya Sumit,
Feferman Leo,
Tobacman Joanne
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1005.2
Subject(s) - sulfotransferase , chondroitin sulfate , chondroitin , chemistry , glycosaminoglycan , wnt signaling pathway , sulfation , extracellular matrix , endocrinology , biochemistry , medicine , biology , signal transduction
Initial experiments in human colonic epithelial cell lines and in the arylsulfatase B (N‐acetylgalactosamine‐4‐sulfatase; ARSB)‐deficient mouse showed that reduction in ARSB and the resultant increase in chondroitin‐4‐sulfate (C4S) were associated with reduction in chondroitin‐4‐sulfotransferase expression and ~50% reduction in sulfotransferase activity with overall increase in total sulfated glycosaminoglycans and C4S. Our experiments have also shown that decline in ARSB leads to increase in Wnt9A expression in human colonic epithelial cells and mouse intestine. Since modeling of the extracellular matrix by Wnt and BMP4 involves their interactions with sulfated glycosaminoglycans, including chondroitin sulfate, we evaluated the interactions among ARSB, Wnt9A, BMP4, and chondroitin‐4‐sulfotransferase (CHST11). Following silencing of Wnt9A by siRNA, the CHST11 expression increased to ~3 times baseline and the sulfotransferase activity increased to ~1.6 times the baseline. In contrast, when BMP4 was neutralized by blocking antibody, the CHST11 expression declined to ~50% of the baseline level. Exogenous administration of BMP4 increased the CHST11 expression to 2‐3 times the baseline level. In ARSB‐deficient mice, the BMP4 expression was ~50% of the value in the wild‐type control, and consistent with a decline in CHST11 expression. Both BMP4 and Wnt exert crucial effects in modeling of the extracellular environment, and these observed opposing effects on CHST11 expression and in relation to ARSB activity may be fundamental to their interaction and to their structural and functional effects.