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The role and regulation of Inhibitor of Differentiation (Id) family members in hypoxic pulmonary hypertension
Author(s) -
Lowery Jonathan Wayne,
Anderson Lynda,
Jones Mark,
Caestecker Mark Peter
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1023.7
Subject(s) - hypoxia (environmental) , pulmonary hypertension , downregulation and upregulation , right ventricular hypertrophy , vascular remodelling in the embryo , transcription factor , muscle hypertrophy , mutant , biology , cancer research , microbiology and biotechnology , endocrinology , medicine , chemistry , genetics , gene , organic chemistry , oxygen
Aberrations in BMP signaling have been implicated in the etiology of Pulmonary Arterial Hypertension. However, the specific role of BMP signaling in the normal pulmonary vasculature is not known. Here, we evaluate the necessity of the downstream BMP target Id1 in the vascular remodeling of murine hypoxic pulmonary hypertension (PH). Id1, which is strongly induced by 1 and 3 weeks hypoxia, is a dominant negative member of the basic helix‐loop‐helix family of transcription factors and promotes cell de‐differentiation, proliferation, and migration. However, we show that wild type, Id1 +/− , and Id1 −/− mutant mice do not differ in the development of hypoxic PH, as determined by increased right ventricular (RV) systolic pressure and RV hypertrophy. Furthermore, loss of Id1 does not lead to defects in hypoxia‐induced proliferation or muscularization of peripheral pulmonary vessels. Upon assessing compensation for loss of Id1 by other Id family members, we found that both Id2 and Id3 are induced by hypoxia and display a partially overlapping expression pattern with Id1. Moreover, expression of Id2 and Id3 are selectively elevated in peripheral vessel vascular smooth muscle cells of Id1 −/− mutant mice. Collectively, our data suggest that, in response to chronic hypoxia, Id1 may promote vascular remodeling, but functional compensation for the loss of Id1 might occur through the upregulation of other Id family members.