P189 IDENTIFYING PTPN14-DEPENDENT MECHANISMS THAT INFLUENCE CLINICAL MANIFESTATIONS OF HEREDITARY HEMORRHAGIC TELANGIECTASIA

DOI

10.1016/j.artres.2017.10.190How to use a DOI?

Abstract

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder caused predominantly by loss of a single allele of ENG (HHT1) or ACVRL1 (HHT2). Global incidence is about 1 in 5,000. Clinical manifestations include cutaneous, mucosal and/or gastrointestinal (GI) tract telangiectases that can cause severe epistaxis or GI bleeding. Some patients (10–50%) develop arteriovenous malformations (AVMs) in the lung, brain or liver. We previously showed that genetic variants of PTPN14 (Phospho-Tyrosine Phosphatase Non-Receptor Type 14) genetically associate with the presence of lung AVMs. Homozygous loss of PTPN14 has also been reported to cause lymphedema due to lymph EC hyperplasia.

Other studies, in tumor epithelial cells, show that PTPN14 can dephosphorylate b- catenin, modulate HIPPO signaling and regulate tyrosine kinase receptor turnover through endosomal pathways.

To investigate its role in ECs and its interactions with the endoglin/ACVRL1 axis, we studied the effect of PTPN14 knock down on differential expression of components of BMP9 and TGF-b signaling pathways in primary human umbilical artery ECs (HUAEC). PTPN14 expression had no effect on pSmad2/3 or pSmad1/5/8 activation but affected protein levels of VEGFR2 and EphrinB2. PTPN14 may thus act on a network of interacting signaling pathways, including endoglin and ACVRL1, by regulating cell surface receptor presentation and endocytic turnover.

Studies are ongoing to address this issue in greater molecular detail. Elucidating the molecular mechanisms involved should contribute to a better understanding of the molecular pathology of HHT, and the regulation of angiogenesis versus stabilization of the vascular bed.

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TY  - JOUR
AU  - Ons Mamai
PY  - 2017
DA  - 2017/12/06
TI  - P189 IDENTIFYING PTPN14-DEPENDENT MECHANISMS THAT INFLUENCE CLINICAL MANIFESTATIONS OF HEREDITARY HEMORRHAGIC TELANGIECTASIA
JO  - Artery Research
SP  - 108
EP  - 108
VL  - 20
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2017.10.190
DO  - 10.1016/j.artres.2017.10.190
ID  - Mamai2017
ER  -