title: Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury.
abstract: Galectin-3 is a β-galactoside binding lectin with roles in diverse processes including proliferation, apoptosis, inflammation and fibrosis which are dependent on different domains of the molecule and subcellular distribution. Although galectin-3 is known to be upregulated in acute kidney injury, the relative importance of its different domains and functions are poorly understood in the underlying pathogenesis. Therefore we experimentally modulated galectin-3 in folic acid (FA)-induced acute kidney injury utilising modified citrus pectin (MCP), a derivative of pectin which can bind to the galectin-3 carbohydrate recognition domain thereby predominantly antagonising functions linked to this role. Mice were pre-treated with normal or 1% MCP-supplemented drinking water one week before FA injection. During the initial injury phase, all FA-treated mice lost weight whilst their kidneys enlarged secondary to the renal insult; these gross changes were significantly lessened in the MCP group but this was not associated with significant changes in galectin-3 expression. At a histological level, MCP clearly reduced renal cell proliferation but did not affect apoptosis. Later, during the recovery phase at two weeks, MCP-treated mice demonstrated reduced galectin-3 in association with decreased renal fibrosis, macrophages, pro-inflammatory cytokine expression and apoptosis. Other renal galectins, galectin-1 and -9, were unchanged. Our data indicates that MCP is protective in experimental nephropathy with modulation of early proliferation and later galectin-3 expression, apoptosis and fibrosis. This raises the possibility that MCP may be a novel strategy to reduce renal injury in the long term, perhaps via carbohydrate binding-related functions of galectin-3.
authors.affiliation: Nephro-Urology Unit, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Kolatsi-Joannou
authors.forename: Karen L
authors.initials: KL
authors.lastname: Price
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Winyard
authors.forename: David A
authors.initials: DA
authors.lastname: Long
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D005492:Folic Acid; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D007677:Kidney Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010368:Pectins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D037502:Galectin 3; D010368:Pectins; D005492:Folic Acid