Università degli Studi di Udine OpenUniud - Archivio istituzionale delle tesi di dottorato
 

OpenUniud - Archivio istituzionale delle tesi di dottorato >
Udine Thesis Repository >
01 - Tesi di dottorato >

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10990/843

Autori: Sartori , Giulio
Supervisore non afferente all'Università: COLOMBATTI, ALFONSO
Centro di ricerca: DIPARTIMENTO DI AREA MEDICA - DAME
Titolo: The interaction between EMILIN1 and α4β1 integrin: molecular mechanisms, colitis and inflammation-associated colorectal carcinogenesis
Abstract (in inglese): The extracellular matrix protein EMILIN1 is the most extensively studied member of the elastin microfibrillar interface proteins (EMILINs) both from the structural and functional point of view. The structure of the gC1q of EMILIN1 solved by NMR highlights unique characteristics compared to other gC1q domains: the residue E933 is the only responsible of the interaction between gC1q and α4β1 and, contrary to integrin occupancy that usually up-regulates cell growth, when gC1q is ligated by the integrin the cells reduce their proliferative activity. My thesis focuses on this function and, in vitro, I demonstrated that EMILIN1 wild type transfected human SK-LMS-1 fibroblasts presented a lower proliferation rate compared to mutant E993A clones. The integrin α4 expressed on fibroblasts interacted with the gC1q and determined a reduced proliferation. Furthermore the gC1q domain exerted an anti-proliferative activity also for α4 transfected colon cancer derived cells. I planned a DSS induced colitis experiment and a two steps colon carcinogenesis model (AOM plus DSS) to demonstrate that the lack of the interaction between EMILIN1 and α4 determined an enhanced proliferation also in vivo in a transgenic mouse where the gC1q domain of EMILIN1 had the E933A mutation, thus not able to interact with α4. I determined the quality and quantity of inflammation in the colitis model, during acute and chronic DSS treatment, and demonstrated that E933A transgenic mice present a much more severe clinical and endoscopic inflammatory disease with a hyper-inflammatory status likely linked to an elevated CD8 T cells although, quite surprisingly, they were much less prone to tumor development compared to wild type littermates.
Parole chiave: Extracellular Matrix; EMILIN1; α4β1 integrin; RAS-ERK pathway; Colitis; Inflammation-associated colorectal carcinogenesis
MIUR : Settore BIO/11 - Biologia Molecolare
Settore MED/04 - Patologia Generale
Lingua: eng
Data: 20-apr-2017
Corso di dottorato: Dottorato di ricerca in Scienze biomediche e biotecnologiche
Ciclo di dottorato: 28
Università di conseguimento titolo: Università degli Studi di Udine
Luogo di discussione: Udine
Altre informazioni: Struttura di aggregazione: Oncologia Sperimentale 2. Centro di Riferimento Oncologico/CRO di Aviano (PN)
Citazione: Sartori, G. The interaction between EMILIN1 and α4β1 integrin: molecular mechanisms, colitis and inflammation-associated colorectal carcinogenesis. (Doctoral Thesis, Università degli Studi di Udine, 2017).
In01 - Tesi di dottorato

Full text:

File Descrizione DimensioniFormatoConsultabilità
SARTORI GIULIO - PhD THESIS PDF:A.pdfTesi dottorato - Sartori Giulio 2,56 MBAdobe PDFVisualizza/apri


Tutti i documenti archiviati in DSPACE sono protetti da copyright. Tutti i diritti riservati.


Segnala questo record su
Del.icio.us

Citeulike

Connotea

Facebook

Stumble it!

reddit


 

  ICT Support, development & maintenance are provided by CINECA. Powered on DSpace SoftwareFeedback CINECA