Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease.
Several lines of evidence implicate the beta-galactoside-binding lectin galectin-3 in development and pathological processes in renal collecting ducts: galectin-3 is expressed in the ureteric bud/collecting duct lineage during nephrogenesis, modulates collecting duct growth/differentiation in vitro, and is expressed in human autosomal recessive polycystic kidney disease in cyst epithelia, almost all of which arise from collecting ducts. Moreover, exogenous galectin-3 restricts growth of cysts generated by Madin-Darby canine kidney collecting duct-derived cells in three-dimensional culture in collagen. Using the cpk mouse model of recessively inherited polycystic kidney disease, we observed widespread galectin-3 mRNA and protein in cyst epithelia. Exogenous galectin-3 reduced cyst formation in suspension culture, and mice-null mutant for galectin-3 had more extensive renal cysts in vivo. Galectin-3 was also detected for the first time in the centrosome/primary cilium, which has been implicated in diverse polycystic kidney disease. Cilia structure/number appeared normal in galectin-3-null mutants. Finally, paclitaxel, a therapy that retards polycystic kidney disease in cpk mice, increased extracellular galectin-3, in which the lectin could potentially interact with cilia. These data raise the possibility that galectin-3 may act as a natural brake on cystogenesis in cpk mice, perhaps via ciliary roles.
Chiu
Miliyun G
MG
Nephro-Urology Unit, UCL Institute of Child Health, 30 Guilford St., London WC1N 1EH, UK.
Johnson
Tanya M
TM
Woolf
Adrian S
AS
Dahm-Vicker
Eugenia M
EM
Long
David A
DA
Guay-Woodford
Lisa
L
Hillman
Katherine A
KA
Bawumia
Suleman
S
Venner
Kerrie
K
Hughes
R Colin
RC
Poirier
Francoise
F
Winyard
Paul J D
PJ
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D003560:Cysts / Q000473:pathology*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000494:pharmacology*; D007690:Polycystic Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D037502:Galectin 3; D017239:Paclitaxel