RhoB is Associated with the Anti-angiogenic Effects of Celiac Patient Transglutaminase 2-targeted Autoantibodies

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2012 Jan 7

PMID 22223195

Citations 9

Authors

Stefania Martucciello

Miha Lavric

Boglarka Toth

Toth Boglarka

Ilma Korponay-Szabo

Cristina Nadalutti

Essi Myrsky

Tiina Rauhavirta

Carla Esposito

Ana-Marija Sulic

Daniele Sblattero

Roberto Marzari

Markku Maki

Katri Kaukinen

Katri Lindfors

Sergio Caja

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement.

Discepolo V, Lania G, Ten Eikelder M, Nanayakkara M, Sepe L, Tufano R Int J Mol Sci. 2021; 22(5).

PMID: 33800150 PMC: 7962447. DOI: 10.3390/ijms22052708.

Interplay between Type 2 Transglutaminase (TG2), Gliadin Peptide 31-43 and Anti-TG2 Antibodies in Celiac Disease.

Martucciello S, Sposito S, Esposito C, Paolella G, Caputo I Int J Mol Sci. 2020; 21(10).

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Constitutive Differential Features of Type 2 Transglutaminase in Cells Derived from Celiac Patients and from Healthy Subjects.

Paolella G, Nanayakkara M, Sposito S, Lepretti M, Auricchio S, Esposito C Int J Mol Sci. 2020; 21(4).

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