Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an XXXX -dependent mechanism.

@entity32 @entity7312 @entity63 @entity19 @entity9701 @entity810 @entity25694 @entity48353
Tamm-Horsfall protein ( @entity7312 ) is a glycoprotein expressed exclusively in thick ascending limbs (TAL) of the kidney. We recently described a novel protective role of @entity7312 against @entity810 ( @entity810 ) via downregulation of @entity32 in the outer medulla. Our current study investigates the mechanistic relationships among the status of @entity7312 , @entity32 , and @entity810 . Using an @entity63 -reperfusion model in wild-type and @entity7312 -/- @entity19 , we demonstrate that it is the S3 proximal segments but not the @entity7312 -deficient TAL that are the main targets of @entity810 during @entity810 . The injured S3 segments that are surrounded by neutrophils in @entity7312 -/- @entity19 have marked overexpression of neutrophil chemoattractant @entity9701 compared with wild-type counterparts. Neutralizing @entity9701 ( @entity9701 ) antibody rescues S3 segments from injury, decreases neutrophil infiltration, and improves kidney function in @entity7312 -/- @entity19 . Furthermore, using immunofluorescence volumetric imaging of wild-type @entity19 kidneys, we show that @entity63 alters the intracellular translocation of @entity7312 in the TAL cells by partially shifting it from its default apical surface domain to the basolateral domain, the latter being contiguous to the basolateral surface of S3 segments. Concomitant with this is the upregulation, in the basolateral surface of S3 segments, of the scavenger receptor @entity25694 , a putative receptor for @entity7312 . We conclude that @entity48353 affects the susceptibility of S3 segments to injury at least in part by regulating @entity9701 expression in a @entity7312 -dependent manner. Our findings raise the interesting possibility of a direct role of basolaterally released @entity7312 on regulating @entity32 in S3 segments.
