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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2011 ; 300
(4
): F999-1007
Nephropedia Template TP
gab.com Text
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English Wikipedia
Tamm-Horsfall protein-deficient thick ascending limbs promote injury to
neighboring S3 segments in an MIP-2-dependent mechanism
#MMPMID21228114
El-Achkar TM
; McCracken R
; Rauchman M
; Heitmeier MR
; Al-Aly Z
; Dagher PC
; Wu XR
Am J Physiol Renal Physiol
2011[Apr]; 300
(4
): F999-1007
PMID21228114
show ga
Tamm-Horsfall protein (THP) is a glycoprotein expressed exclusively in thick
ascending limbs (TAL) of the kidney. We recently described a novel protective
role of THP against acute kidney injury (AKI) via downregulation of inflammation
in the outer medulla. Our current study investigates the mechanistic
relationships among the status of THP, inflammation, and tubular injury. Using an
ischemia-reperfusion model in wild-type and THP-/- mice, we demonstrate that it
is the S3 proximal segments but not the THP-deficient TAL that are the main
targets of tubular injury during AKI. The injured S3 segments that are surrounded
by neutrophils in THP-/- mice have marked overexpression of neutrophil
chemoattractant MIP-2 compared with wild-type counterparts. Neutralizing
macrophage inflammatory protein-2 (MIP-2) antibody rescues S3 segments from
injury, decreases neutrophil infiltration, and improves kidney function in THP-/-
mice. Furthermore, using immunofluorescence volumetric imaging of wild-type mouse
kidneys, we show that ischemia alters the intracellular translocation of THP 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 SRB-1, a putative receptor for
THP. We conclude that TAL affects the susceptibility of S3 segments to injury at
least in part by regulating MIP-2 expression in a THP-dependent manner. Our
findings raise the interesting possibility of a direct role of basolaterally
released THP on regulating inflammation in S3 segments.