An Essential Role for Resident Fibroblasts in Experimental Lung Fibrosis Is Defined by Lineage-Specific Deletion of High-Affinity Type II Transforming Growth Factor β Receptor

Abstract

Intact TGFβ signaling in resident pulmonary fibroblasts is essential for pulmonary fibrosis to develop. Our data support a key regulatory role of these cells in determining fibrocyte recruitment and myofibroblast differentiation.

Pulmonary fibrosis: tissue characterization using late-enhanced MRI compared with unenhanced anatomic high-resolution CT

“…In disease states fibroblast activity becomes deregulated in entities such as IPF and cardiac fibrosis, producing a pathologic fibrotic response. Fibroblast proliferation is particularly well validated in lung fibrosis using lineage-specific deletion of the type II transforming growth factor beta (TGF-β) receptor (23). Transforming growth factor beta (TGF-β) receptor is also widely implicated in the increased expression of fibroblasts in cardiac fibrosis (24).…”

Update in Diffuse Parenchymal Lung Disease 2011

“…Work by Hoyles and colleagues highlights a central role of TGF-b signaling by demonstrating that signaling via the highaffinity type II TGF-b receptors is important in fibrocyte recruitment in addition to myofibroblast differentiation and matrix production of lung resident fibroblasts in a mouse model of fibrosis (45). Lin and colleagues demonstrated that the activity of transcription factor Yin Yang 1 (YY1) in fibroblasts promotes fibrogenesis by increasing myofibroblast differentiation and collagen production (46).…”

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

“…Many hypotheses have been proposed regarding the cellular origin of activated myofibroblasts in IPF. One hypothesis is that they originate from resident fibroblasts expressing high-affinity type 2 TGFβ receptor (Hoyles et al, 2011). Other studies investigated the possibility that they originate from bone-marrow-derived CD45 + COL1 + CXCR4 + circulating fibrocytes (Phillips et al, 2004) that are recruited to the lungs.…”