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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Med 2015 ; 21 (9): 998-1009 Nephropedia Template TP
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Epithelial to Mesenchymal Transition induces cell cycle arrest and parenchymal damage in renal fibrosis #MMPMID26236991
Nat Med 2015[Sep]; 21 (9): 998-1009 PMID26236991show ga
Kidney fibrosis is marked by an epithelial?to?mesenchymal transition (EMT) by 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 EMT program during fibrotic injury is an arrest in the G2 phase of the cell cycle and lower expression of several transporters in TECs. We also found that transgenic expression of Twist or Snai1 expression is sufficient to promote prolonged TGF-?1?induced G2 arrest of TECs, limiting their potential for repair and regeneration. Also, 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 restoring proliferation, de?differentiation?associated repair and regeneration of the kidney parenchyma and attenuating interstitial fibrosis. Thus, inhibition of EMT program in TECs during chronic renal injury represents a potential anti?fibrosis therapy