Objective— Circulating angiogenic cells (CACs) expansion is a multistage process requiring sequential activation of transcriptional factors, including STAT5. STAT5, in concert with peroxisome proliferator-activated receptors (PPARs), seems to induce discrete biological responses in different tissues. In the present study we investigated the role of STAT5 and PPAR{gamma} in regulating CAC expansion in normal and diabetic settings. Methods and Results— Normal and diabetic CACs were used. siRNA technology, EMSA, and chromatin immunoprecipitation (ChIP) assay as well as site-directed mutagenesis of the STAT5 response element in the PPAR{gamma} promoter enabled us to demonstrate that STAT5 transcriptional activity controls PPAR{gamma} expression. Moreover, FACS analysis, coimmunoprecipitation experiments, and ChIP assay revealed that a STAT5/PPAR{gamma} transcriptional complex controls cyclin D1 expression and CAC progression into the cell-cycle. Conversely, PPAR{gamma} agonists, by preventing the expression of STAT5 and the formation of the STAT5/PPAR{gamma} heterodimeric complex failed to promote CAC expansion. Finally, we demonstrated that diabetic CAC functional capability can be recovered by molecules able to activate the STAT5/PPAR{gamma} transcriptional complex. Conclusions— Our data identify the STAT5/PPAR{gamma} heterodimers as landmark of CAC expansion and provide evidences for a mechanism that partially rescues CAC bioavailability in diabetic setting.

Formation of STAT5/PPAR{gamma} Transcriptional Complex Modulates Angiogenic Cell Bioavailability in Diabetes

DENTELLI, Patrizia;TROMBETTA, Antonella;TOGLIATTO, Gabriele Maria;ROSSO, Arturo;UBERTI, BARBARA;ORSO, FRANCESCA;TAVERNA, Daniela;PEGORARO, Luigi;BRIZZI, Maria Felice
2009-01-01

Abstract

Objective— Circulating angiogenic cells (CACs) expansion is a multistage process requiring sequential activation of transcriptional factors, including STAT5. STAT5, in concert with peroxisome proliferator-activated receptors (PPARs), seems to induce discrete biological responses in different tissues. In the present study we investigated the role of STAT5 and PPAR{gamma} in regulating CAC expansion in normal and diabetic settings. Methods and Results— Normal and diabetic CACs were used. siRNA technology, EMSA, and chromatin immunoprecipitation (ChIP) assay as well as site-directed mutagenesis of the STAT5 response element in the PPAR{gamma} promoter enabled us to demonstrate that STAT5 transcriptional activity controls PPAR{gamma} expression. Moreover, FACS analysis, coimmunoprecipitation experiments, and ChIP assay revealed that a STAT5/PPAR{gamma} transcriptional complex controls cyclin D1 expression and CAC progression into the cell-cycle. Conversely, PPAR{gamma} agonists, by preventing the expression of STAT5 and the formation of the STAT5/PPAR{gamma} heterodimeric complex failed to promote CAC expansion. Finally, we demonstrated that diabetic CAC functional capability can be recovered by molecules able to activate the STAT5/PPAR{gamma} transcriptional complex. Conclusions— Our data identify the STAT5/PPAR{gamma} heterodimers as landmark of CAC expansion and provide evidences for a mechanism that partially rescues CAC bioavailability in diabetic setting.
2009
29
114
120
transcriptional factors; STAT5; PPARgamma; angiogenic cells; diabetes
Patrizia Dentelli; Antonella Trombetta; Gabriele Togliatto; Annarita Zeoli; Arturo Rosso; Barbara Uberti; Francesca Orso; Daniela Taverna; Luigi Pegor...espandi
File in questo prodotto:
File Dimensione Formato  
ATVB 2009.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 1.1 MB
Formato Adobe PDF
1.1 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/59128
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 17
social impact