Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis

Mitsuhiro Matsuda, Kenichi Shikata, Fujio Shimizu, Yasuo Suzuki, Masayuki Miyasaka, Hiroshi Kawachi, Hiroto Kawashima, Jun Wada, Hikaru Sugimoto, Yasushi Shikata, Daisuke Ogawa, Shinichiro J. Tojo, Kazuo Akima, Hirofumi Makino

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The initial event in the process of leukocyte infiltration is characterized by leukocyte rolling on the surface of the endothelium, which is mediated by selectins. P- and L-selectin bind to the sulphated sugar chains of their natural ligands, including sulphated glycolipids such as sulphatide. Recently, it has been demonstrated that sulphated glycolipids and sulphated oligosaccharides interfere with selectin binding pathways. This study synthesized sulphated hyaluronic acid (SHA), which is a potential selectin-blocking agent, and examined its therapeutic effect on the experimental progressive mesangial proliferative glomerulonephritis induced by anti-Thy-1 monoclonal antibody (1-22-3 MAb) after unilateral nephrectomy. The selectin-inhibitory effect of SHA in vitro was confirmed. SHA inhibited the binding of P- and L-selectin to sulphatide, which is a glycolipid ligand for P- and L-selectin, at a concentration of 1.5 μg/ml and 100 μg/ml. Immunohistochemical examination showed that P-selectin was up-regulated in the glomeruli in the 1-22-3 MAb nephritis model, while the ligands for L-selectin were not detected in the glomerular tufts. A single administration of SHA ameliorated proteinuria and glomerular leukocyte infiltration in 24 h after the injection of anti-Thy-1 MAb. Anti-P-selectin MAb, but not anti-L-selectin MAb, inhibited proteinuria and glomerular leukocyte infiltration. To examine further the therapeutic effect of SHA on chronic glomerulonephritis, SHA was administered daily from day 3 to day 14 in this model. Proteinuria and glomerular leukocyte infiltration were significantly diminished in SHA-treated rats on day 14. These results suggest that SHA ameliorated rat progressive mesangial proliferative glomerulonephritis by inhibiting P-selectin-dependent leukocyte infiltration in glomeruli. Sulphated oligosaccharides may be beneficial for the therapy of mesangial proliferative glomerulonephritis.

Original languageEnglish
Pages (from-to)407-414
Number of pages8
JournalJournal of Pathology
Volume198
Issue number3
DOIs
Publication statusPublished - Nov 1 2002

    Fingerprint

Keywords

  • Glomerulonephritis
  • L-selectin
  • Oligosaccharide
  • P-selectin
  • Thy-1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Matsuda, M., Shikata, K., Shimizu, F., Suzuki, Y., Miyasaka, M., Kawachi, H., Kawashima, H., Wada, J., Sugimoto, H., Shikata, Y., Ogawa, D., Tojo, S. J., Akima, K., & Makino, H. (2002). Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis. Journal of Pathology, 198(3), 407-414. https://doi.org/10.1002/path.1209