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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 J+Am+Soc+Nephrol
2014 ; 25
(12
): 2835-46
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Autophagy regulates TGF-? expression and suppresses kidney fibrosis induced by
unilateral ureteral obstruction
#MMPMID24854279
Ding Y
; Kim Sl
; Lee SY
; Koo JK
; Wang Z
; Choi ME
J Am Soc Nephrol
2014[Dec]; 25
(12
): 2835-46
PMID24854279
show ga
Autophagy is an evolutionarily conserved process that cells use to degrade and
recycle cellular proteins and remove damaged organelles. During the past decade,
there has been a growing interest in defining the basic cellular mechanism of
autophagy and its roles in health and disease. However, the functional role of
autophagy in kidney fibrosis remains poorly understood. Here, using GFP-LC3
transgenic mice, we show that autophagy is induced in renal tubular epithelial
cells (RTECs) of obstructed kidneys after unilateral ureteral obstruction (UUO).
Deletion of LC3B (LC3(-/-) mice) resulted in increased collagen deposition and
increased mature profibrotic factor TGF-? levels in obstructed kidneys. Beclin 1
heterozygous (beclin 1(+/-)) mice also displayed increased collagen deposition in
the obstructed kidneys after UUO. We also show that TGF-?1 induces autophagy in
primary mouse RTECs and human renal proximal tubular epithelial (HK-2) cells. LC3
deficiency resulted in increased levels of mature TGF-? in primary RTECs. Under
conditions of TGF-?1 stimulation and autoinduction, inhibition of autolysosomal
protein degradation by bafilomycin A1 increased mature TGF-? protein levels
without alterations in TGF-?1 mRNA. These data suggest a novel intracellular
mechanism by which mature TGF-?1 protein levels may be regulated in RTECs through
autophagic degradation, which suppresses kidney fibrosis induced by UUO. The dual
functions of TGF-?1, as an inducer of TGF-?1 autoinduction and an inducer of
autophagy and TGF-? degradation, underscore the multifunctionality of TGF-?1.