PMID- 22169004
OWN - NLM
STAT- MEDLINE
DCOM- 20120509
LR  - 20211021
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 302
IP  - 6
DP  - 2012 Mar 15
TI  - A novel U-STAT3-dependent mechanism mediates the deleterious effects of chronic 
      nicotine exposure on renal injury.
PG  - F722-9
LID - 10.1152/ajprenal.00338.2011 [doi]
AB  - Previous data from our group have demonstrated (Arany I, Grifoni S, Clark JS, 
      Csongradi, Maric C, Juncos LA. Am J Physiol Renal Physiol 301: F125-F133, 2011) 
      that chronic nicotine (NIC) exposure exacerbates acute renal ischemic injury 
      (AKI) in mice that could increase the risk for development and progression of 
      chronic kidney disease (CKD). It has been shown that proximal tubules of the 
      kidney can acquire characteristics that may compromise structural recovery and 
      favor development of inflammation and fibrosis following injury. Chronic NIC 
      exposure can amplify this epithelial process although the mechanism is not 
      identified. Recently, the unphosphorylated form of signal transducer and 
      activator of transcription-3 (U-STAT3) has emerged as a noncanonical mediator of 
      inflammation and fibrosis that may be responsible for the effects of chronic NIC. 
      We found that levels of transforming growth factor beta-1 (TGF-beta1), alpha-smooth muscle 
      actin (alpha-SMA), fibronectin, monocyte chemotactic protein-1 (MCP-1), and 
      expression of U-STAT3 were increased in the ischemic kidneys of NIC-exposed mice. 
      Chronic NIC exposure also increased TGF-beta1-dependent F-actin reorganization, 
      vimentin, fibronectin, and alpha-SMA expression as well as promoter activity of alpha-SMA 
      and MCP-1 without significant loss of epithelial characteristics (E-cadherin) in 
      cultured renal proximal tubule cells. Importantly, transduction of cells with a 
      U-STAT3 mimetic (Y705F-STAT3) augmented stress fiber formation and also amplified 
      NIC+TGF-beta1-induced expression of alpha-SMA, vimentin, fibronectin, as well as 
      promoter activity of alpha-SMA and MCP-1. Our results reveal a novel, chronic 
      NIC-exposure-related and U-STAT3-dependent mechanism as mediator of a sustained 
      transcription of genes that are linked to remodeling and inflammation in the 
      kidney during injury. This process may facilitate progression of AKI to CKD. The 
      obtained data may lead to devising therapeutic methods to specifically enhance 
      the protective and/or inhibit adverse effects of STAT3 in the kidney.
FAU - Arany, Istvan
AU  - Arany I
AD  - Department of Pediatrics, Division of Pediatric Nephrology, University of 
      Mississippi Medical Center, Research Wing, Rm. R127, 2500 N. State St., Jackson, 
      MS 39216, USA. iarany@umc.edu
FAU - Reed, Dustin K
AU  - Reed DK
FAU - Grifoni, Samira C
AU  - Grifoni SC
FAU - Chandrashekar, Kiran
AU  - Chandrashekar K
FAU - Booz, George W
AU  - Booz GW
FAU - Juncos, Luis A
AU  - Juncos LA
LA  - eng
GR  - R01 HL088101-05/HL/NHLBI NIH HHS/United States
GR  - R01HL088101-02S1/HL/NHLBI NIH HHS/United States
GR  - R01HL088101-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL088101/HL/NHLBI NIH HHS/United States
GR  - DK073401/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111214
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Actins)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Actins
MH  - Animals
MH  - Biomarkers
MH  - Cytokines/genetics/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Kidney/metabolism/pathology
MH  - Kidney Diseases/*chemically induced/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nicotine/administration & dosage/*toxicity
MH  - Phosphorylation
MH  - STAT3 Transcription Factor/genetics/*metabolism
MH  - Transforming Growth Factor beta1/metabolism
PMC - PMC3311312
EDAT- 2011/12/16 06:00
MHDA- 2012/05/10 06:00
PMCR- 2013/03/15
CRDT- 2011/12/16 06:00
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/05/10 06:00 [medline]
PHST- 2013/03/15 00:00 [pmc-release]
AID - ajprenal.00338.2011 [pii]
AID - F-00338-2011 [pii]
AID - 10.1152/ajprenal.00338.2011 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2012 Mar 15;302(6):F722-9. doi: 
      10.1152/ajprenal.00338.2011. Epub 2011 Dec 14.