Galectin-3 preserves renal tubules and modulates extracellular matrix remodeling in progressive fibrosis.
Renal tubular cell apoptosis is a critical detrimental event that leads to chronic kidney injury in association with renal fibrosis. The present study was designed to investigate the role of galectin-3 (Gal-3), an important regulator of multiple apoptotic pathways, in chronic kidney disease induced by unilateral ureteral obstruction (UUO). After UUO, Gal-3 expression significantly increased compared with basal levels reaching a peak increase of 95-fold by day 7. Upregulated Gal-3 is predominantly tubular at early time points after UUO but shifts to interstitial cells as the injury progresses. On day 14, there was a significant increase in TdT-mediated dUTP nick end labeling-positive cells (129%) and cytochrome c release (29%), and a decrease in BrdU-positive cells (62%) in Gal-3-deficient compared with wild-type mice. The degree of renal damage was more extensive in Gal-3-deficient mice at days 14 and 21, 35 and 21% increase in total collagen, respectively. Despite more severe fibrosis, myofibroblasts were significantly decreased by 58% on day 14 in the Gal-3-deficient compared with wild-type mice. There was also a corresponding 80% decrease in extracellular matrix synthesis in Gal-3-deficient compared with wild-type mice. Endo180 is a recently recognized receptor for intracellular collagen degradation that is expressed by interstitial cells during renal fibrogenesis. Endo180 expression was significantly decreased by greater than 50% in Gal-3-deficient compared with wild-type mice. Taken together, these results suggested that Gal-3 not only protects renal tubules from chronic injury by limiting apoptosis but that it may lead to enhanced matrix remodeling and fibrosis attenuation.
Department of Pediatrics, Seattle Children's Research Institute, University of Washington, Division of Nephrology, 4800 Sand Point Way NE, A7931, Seattle, WA 98105, USA. daryl.okamura@seattlechildrens.org
Daryl M
DM
Okamura
Katie
K
Pasichnyk
Jesus M
JM
Lopez-Guisa
Sarah
S
Collins
Daniel K
DK
Hsu
Fu-Tong
FT
Liu
Allison A
AA
Eddy
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis; D037502:Galectin 3 / Q000172:deficiency / Q000502:physiology*; D007674:Kidney Diseases / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D058628:Myofibroblasts / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications
D037502:Galectin 3; D008562:Membrane Glycoproteins; C474081:Mrc2 protein, mouse; D011956:Receptors, Cell Surface