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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
2008 ; 295
(2
): F534-44
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing
inflammation and altering TLR4 expression
#MMPMID18495803
El-Achkar TM
; Wu XR
; Rauchman M
; McCracken R
; Kiefer S
; Dagher PC
Am J Physiol Renal Physiol
2008[Aug]; 295
(2
): F534-44
PMID18495803
show ga
Tamm-Horsfall protein (THP) is a glycoprotein with unclear functions expressed
exclusively in thick ascending limbs (TAL) of the kidney. Its role in ischemic
acute kidney injury is uncertain, with previous data suggesting a possible
negative effect by enhancing cast formation and promoting inflammation. Using a
recently characterized THP knockout mouse (THP-/-), we investigated the role of
THP in renal ischemia-reperfusion injury (IRI). In wild-type mice (THP+/+), THP
expression was increased by injury. THP-/- mice developed more functional and
histological renal damage after IRI compared with THP+/+. THP-/- kidneys showed
more inflammation and tubular necrosis. Cast formation correlated with the
severity of injury and was independent of THP presence. THP absence was
associated with a more necrotic, rather than apoptotic, phenotype of cell death.
The outer medulla was predominantly affected, where significant interstitial
neutrophil infiltration was detected in proximity to injured S3 proximal tubular
segments and TAL. This coincided with an enhanced expression of the innate
immunity receptor Toll-like receptor 4 (TLR4) in S3 segments of THP-/- compared
with THP+/+ mice. Specifically, a basolateral S3 expression of TLR4 was more
evident in THP-/- kidneys compared with a more apical distribution in THP+/+.
Such basolateral location for TLR4 allows a greater interaction with
proinflammatory ligands present in the interstitium during ischemia. In
conclusion, we are showing a completely novel role for a very old protein in the
setting of renal injury. Our data suggest that THP stabilizes the outer medulla
in the face of injury by decreasing inflammation, possibly through an effect on
TLR4.