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.
Okamura
Daryl M
DM
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
Pasichnyk
Katie
K
Lopez-Guisa
Jesus M
JM
Collins
Sarah
S
Hsu
Daniel K
DK
Liu
Fu-Tong
FT
Eddy
Allison A
AA
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