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Angiotensin II contributes to renal fibrosis independently of Notch pathway activation.
PLoS One. 2012; 7(7):e40490.Plos

Abstract

Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression.

Authors+Show Affiliations

Cellular Biology in Renal Diseases Laboratory, Universidad Autónoma, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22792351

Citation

Lavoz, Carolina, et al. "Angiotensin II Contributes to Renal Fibrosis Independently of Notch Pathway Activation." PloS One, vol. 7, no. 7, 2012, pp. e40490.
Lavoz C, Rodrigues-Diez R, Benito-Martin A, et al. Angiotensin II contributes to renal fibrosis independently of Notch pathway activation. PLoS One. 2012;7(7):e40490.
Lavoz, C., Rodrigues-Diez, R., Benito-Martin, A., Rayego-Mateos, S., Rodrigues-Diez, R. R., Alique, M., Ortiz, A., Mezzano, S., Egido, J., & Ruiz-Ortega, M. (2012). Angiotensin II contributes to renal fibrosis independently of Notch pathway activation. PloS One, 7(7), e40490. https://doi.org/10.1371/journal.pone.0040490
Lavoz C, et al. Angiotensin II Contributes to Renal Fibrosis Independently of Notch Pathway Activation. PLoS One. 2012;7(7):e40490. PubMed PMID: 22792351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II contributes to renal fibrosis independently of Notch pathway activation. AU - Lavoz,Carolina, AU - Rodrigues-Diez,Raquel, AU - Benito-Martin,Alberto, AU - Rayego-Mateos,Sandra, AU - Rodrigues-Diez,Raúl R, AU - Alique,Matilde, AU - Ortiz,Alberto, AU - Mezzano,Sergio, AU - Egido,Jesús, AU - Ruiz-Ortega,Marta, Y1 - 2012/07/09/ PY - 2012/02/27/received PY - 2012/06/08/accepted PY - 2012/7/14/entrez PY - 2012/7/14/pubmed PY - 2013/1/11/medline SP - e40490 EP - e40490 JF - PloS one JO - PLoS One VL - 7 IS - 7 N2 - Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22792351/Angiotensin_II_contributes_to_renal_fibrosis_independently_of_Notch_pathway_activation_ L2 - https://dx.plos.org/10.1371/journal.pone.0040490 DB - PRIME DP - Unbound Medicine ER -