Open AccessHistological hallmarks and role of Slug/ PIP axis in pulmonary hypertension secondary to pulmonary fibrosis
Author(s) -
Ruffenach Gregoire,
Umar Soban,
Vaillancourt Mylene,
Hong Jason,
Cao Nancy,
Sarji Shervin,
Moazeni Shayan,
Cunningham Christine M,
Ardehali Abbas,
Reddy Srinivasa T,
Saggar Rajan,
Fishbein Gregory,
Eghbali Mansoureh
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201810061
Subject(s) - anesthesiology , perioperative medicine , perioperative , medicine , surgery , pathology
Pulmonary hypertension secondary to pulmonary fibrosis ( PF ‐ PH ) is one of the most common causes of PH , and there is no approved therapy. The molecular signature of PF ‐ PH and underlying mechanism of why pulmonary hypertension ( PH ) develops in PF patients remains understudied and poorly understood. We observed significantly increased vascular wall thickness in both fibrotic and non‐fibrotic areas of PF ‐ PH patient lungs compared to PF patients. The increased vascular wall thickness in PF ‐ PH patients is concomitant with a significantly increased expression of the transcription factor Slug within the macrophages and its target prolactin‐induced protein ( PIP ), an extracellular matrix protein that induces pulmonary arterial smooth muscle cell proliferation. We developed a novel translational rat model of combined PF ‐ PH that is reproducible and shares similar histological features (fibrosis, pulmonary vascular remodeling) and molecular features (Slug and PIP upregulation) with human PF ‐ PH . We found Slug inhibition decreases PH severity in our animal model of PF ‐ PH . Our study highlights the role of Slug/ PIP axis in PF ‐ PH .