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1.
001-es BibID:
BIBFORM048568
035-os BibID:
Article ID: e65887
Első szerző:
Kalliokoski, Suvi
Cím:
Celiac Disease-Specific TG2-Targeted Autoantibodies Inhibit Angiogenesis Ex Vivo and In Vivo in Mice by Interfering with Endothelial Cell Dynamics / Suvi Kalliokoski, Ana-Marija Sulic, Ilma R. Korponay-Szabo, Zsuzsa Szondy, Rafael Frias, Mileidys Alea Perez, Stefania Martucciello, Anne Roivainen, Lauri J. Pelliniemi, Carla Esposito, Martin Griffin, Daniele Sblattero, Markku Mäki, Katri Kaukinen, Katri Lindfors, Sergio Caja
Dátum:
2013
ISSN:
1932-6203
Megjegyzések:
A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:
Plos One [electronic resource]. - 8 : 6 (2013), [8] p. -
További szerzők:
Sulic, Ana-Marija
Korponay-Szabó Ilma (1959-) (gyermekgyógyász)
Szondy Zsuzsanna (1959-) (molekuláris sejtbiológus, biokémikus)
Frías, Rafael
Perez, Mileidys Alea
Martucciello, Stefania
Roivainen, Anne
Pelliniemi, Lauri J.
Esposito, Carla
Griffin, Martin
Sblattero, Daniele
Mäki, Markku
Kaukinen, Katri
Lindfors, Katri
Caja, Sergio
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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Saját polcon:
2.
001-es BibID:
BIBFORM044274
Első szerző:
Martucciello, Stefania
Cím:
RhoB is associated with the anti-angiogenic effects of celiac patient transglutaminase 2-targeted autoantibodies / Martucciello Stefania, Lavric Miha, Toth Boglarka, Korponay-Szabo Ilma, Nadalutti Cristina, Myrsky Essi, Rauhavirta Tiina, Esposito Carla, Sulic Ana-Marija, Sblattero Daniele, Marzari Roberto, Mäki Markku, Kaukinen Katri, Lindfors Katri, Caja Sergio
Dátum:
2012
ISSN:
0946-2716
Megjegyzések:
Celiac patient-derived anti-transglutaminase 2 (TG2) antibodies disturb several steps in angiogenesis, but the detailed molecular basis is not known. Therefore, we here analyzed by microarray technology the expression of a set of genes related to angiogenesis and endothelial cell biology in order to identify factors that could explain our previous data related to vascular biology in the context of celiac disease. To this end, in vitro models using human umbilical vein endothelial cells (HUVECs) or in vivo models of angiogenesis were used. A total of 116 genes were analyzed after treatment with celiac patient autoantibodies against TG2. Compared to treatment with control IgA celiac patient, total IgA induced a consistent expression change of 10 genes, the up-regulation of four and down-regulation of six. Of these genes the up-regulated RhoB was selected for further studies. RhoB expression was found to be up-regulated at both messenger RNA and protein level in response to celiac patient total IgA as well as anti-TG2-specific antibody derived from a celiac patient. Interestingly, down-regulation of RhoB by specific small interfering RNA treatment in endothelial cells could rescue the deranged endothelial length and tubule formation caused by celiac disease autoantibodies. RhoB function is controlled by its post-translational modification by farnesylation. This modification of RhoB required for its correct function can be prevented by the cholesterol lowering drug simvastatin, which was also able to abolish the anti-angiogenic effects of celiac anti-TG2 autoantibodies. Taken together, our results would suggest that RhoB plays a key role in the response of endothelial cells to celiac disease-specific anti-TG2 autoantibodies
Tárgyszavak:
Orvostudományok
Klinikai orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:
Journal Of Molecular Medicine-Jmm. - 90 : 7 (2012), p. 817-826. -
További szerzők:
Lavric, Miha
Tóth Boglárka
Korponay-Szabó Ilma (1959-) (gyermekgyógyász)
Nadalutti, Cristina
Myrsky, Essi
Rauhavirta, Tiina
Esposito, Carla
Sulic, Ana-Marija
Sblattero, Daniele
Marzari, Roberto
Mäki, Markku
Kaukinen, Katri
Lindfors, Katri
Caja, Sergio
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
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