Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24652804
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2014 ; 25
(9
): 1966-78
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
TGF-?-activated kinase 1 is crucial in podocyte differentiation and glomerular
capillary formation
#MMPMID24652804
Kim SI
; Lee SY
; Wang Z
; Ding Y
; Haque N
; Zhang J
; Zhou J
; Choi ME
J Am Soc Nephrol
2014[Sep]; 25
(9
): 1966-78
PMID24652804
show ga
TGF-?-activated kinase 1 (TAK1) is a key intermediate in signal transduction
induced by TGF-? or inflammatory cytokines, such as TNF-? and IL-1, which are
potent inducers of podocyte injury responses that lead to proteinuria and
glomerulosclerosis. Nevertheless, little is known about the physiologic and
pathologic roles of TAK1 in podocytes. To examine the in vivo role of TAK1, we
generated podocyte-specific Tak1 knockout mice (Nphs2-Cre(+):Tak1(fx/fx);
Tak1(?/?)). Targeted deletion of Tak1 in podocytes resulted in perinatal
lethality, with approximately 50% of animals dying soon after birth and 90% of
animals dying within 1 week of birth. Tak1(?/?) mice developed proteinuria from
P1 and exhibited delayed glomerulogenesis and reduced expression of Wilms' tumor
suppressor 1 and nephrin in podocytes. Compared with Tak1(fx/fx) mice, Tak1(?/?)
mice exhibited impaired formation of podocyte foot processes that caused
disruption of the podocyte architecture with prominent foot process effacement.
Intriguingly, Tak1(?/?) mice displayed increased expression of vascular
endothelial growth factor within the glomerulus and abnormally enlarged
glomerular capillaries. Furthermore, 4- and 7-week-old Tak1(?/?) mice with
proteinuria had increased collagen deposition in the mesangium and the adjacent
tubulointerstitial area. Thus, loss of Tak1 in podocytes is associated with the
development of proteinuria and glomerulosclerosis. Taken together, our data show
that TAK1 regulates the expression of Wilms' tumor suppressor 1, nephrin, and
vascular endothelial growth factor and that TAK1 signaling has a crucial role in
podocyte differentiation and attainment of normal glomerular microvasculature
during kidney development and glomerular filtration barrier homeostasis.
|Animals
[MESH]
|Animals, Newborn
[MESH]
|Capillaries/enzymology/growth & development
[MESH]
|Cell Differentiation/genetics/physiology
[MESH]
|Collagen/metabolism
[MESH]
|Female
[MESH]
|Glomerular Filtration Barrier/blood supply/enzymology/growth & development
[MESH]
|Kidney Glomerulus/*blood supply/*enzymology/growth & development
[MESH]
free
free
free
