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2014 ; 289
(45
): 31526-33
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Secreted Frizzled-related protein 1 (Sfrp1) regulates the progression of renal
fibrosis in a mouse model of obstructive nephropathy
#MMPMID25253698
Matsuyama M
; Nomori A
; Nakakuni K
; Shimono A
; Fukushima M
J Biol Chem
2014[Nov]; 289
(45
): 31526-33
PMID25253698
show ga
Renal fibrosis is responsible for progressive renal diseases that cause chronic
renal failure. Sfrp1 (secreted Frizzled-related protein 1) is highly expressed in
kidney, although little is known about connection between the protein and renal
diseases. Here, we focused on Sfrp1 to investigate its roles in renal fibrosis
using a mouse model of unilateral ureteral obstruction (UUO). In wild-type mice,
the expression of Sfrp1 protein was markedly increased after UUO. The kidneys
from Sfrp1 knock-out mice showed significant increase in expression of
myofibrobast markers, ?-smooth muscle actin (?SMA). Sfrp1 deficiency also
increased protein levels of the fibroblast genes, vimentin, and decreased those
of the epithelial genes, E-cadherin, indicated that enhanced
epithelial-to-mesenchymal transition. There was no difference in the levels of
canonical Wnt signaling; rather, the levels of phosphorylated c-Jun and JNK were
more increased in the Sfrp1(-/-) obstructed kidney. Moreover, the apoptotic cell
population was significantly elevated in the obstructed kidneys from Sfrp1(-/-)
mice following UUO but was slightly increased in those from wild-type mice. These
results indicate that Sfrp1 is required for inhibition of renal damage through
the non-canonical Wnt/PCP pathway.
|Animals
[MESH]
|Cadherins/metabolism
[MESH]
|Disease Models, Animal
[MESH]
|Disease Progression
[MESH]
|Epithelial-Mesenchymal Transition
[MESH]
|Fibroblasts/metabolism
[MESH]
|Fibrosis/*metabolism
[MESH]
|Gene Deletion
[MESH]
|HEK293 Cells
[MESH]
|Humans
[MESH]
|Intercellular Signaling Peptides and Proteins/*physiology
[MESH]