Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26236991
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal
damage in renal fibrosis
#MMPMID26236991
Lovisa S
; LeBleu VS
; Tampe B
; Sugimoto H
; Vadnagara K
; Carstens JL
; Wu CC
; Hagos Y
; Burckhardt BC
; Pentcheva-Hoang T
; Nischal H
; Allison JP
; Zeisberg M
; Kalluri R
Nat Med
2015[Sep]; 21
(9
): 998-1009
PMID26236991
show ga
Kidney fibrosis is marked by an epithelial-to-mesenchymal transition (EMT) of
tubular epithelial cells (TECs). Here we find that, during renal fibrosis, TECs
acquire a partial EMT program during which they remain associated with their
basement membrane and express markers of both epithelial and mesenchymal cells.
The functional consequence of the EMT program during fibrotic injury is an arrest
in the G2 phase of the cell cycle and lower expression of several solute and
solvent transporters in TECs. We also found that transgenic expression of either
Twist1 (encoding twist family bHLH transcription factor 1, known as Twist) or
Snai1 (encoding snail family zinc finger 1, known as Snail) expression is
sufficient to promote prolonged TGF-?1-induced G2 arrest of TECs, limiting the
cells' potential for repair and regeneration. In mouse models of experimentally
induced renal fibrosis, conditional deletion of Twist1 or Snai1 in proximal TECs
resulted in inhibition of the EMT program and the maintenance of TEC integrity,
while also restoring cell proliferation, dedifferentiation-associated repair and
regeneration of the kidney parenchyma and attenuating interstitial fibrosis.
Thus, inhibition of the EMT program in TECs during chronic renal injury
represents a potential anti-fibrosis therapy.
free
free
free
