Model of elastic fiber formation in control, IPAH and HPAH with a BMPR2 mutation.
While TGFβ1 stimulates elastin mRNA, production of elastin and fibrillin-1 proteins are both largely BMPR2 dependent. TGFβ1 and BMP4 via BMPR2 increase fibrillin-1. In IPAH the elastic fiber formation is impaired due to reduced fibrillin-1 mRNA and protein and elastin mRNA, although some elastin protein is produced in response to TGFβ1. When there is a mutation in BMPR2, fibrillin-1 and elastin protein are both markedly decreased in response to both TGFβ1 and BMP4, leading to poorly assembled elastic fibers.