Pericytes in Chronic Lung Disease

Abstract

Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lung diseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte-to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lung disease and confirm the importance of pericytes in human fibrotic pulmonary disease.

ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling

“…Pericytes were recently determined to exhibit trilineage differentiation properties and colony-forming activity similar to MSC. 9 Intriguingly, a current study showed that perivascular MSC-like Gli1 + cells differentiate into myofibroblasts in response to tissue damage, and contribute to tissue fibrosis. 20 These Gli1 + cells have the ability to gain or loose the NG2 positivity suggesting them to be a differentiation state of pericytes.…”

“…8 Recently, pericytes have been suggested to be a type of mesenchymal stem cells (MSCs) due to their capacity to differentiate into osteoblasts, chondrocytes, and adipocytes. 9 An important regulator of stem cell homeostasis is the Wingless/Integrase-1 (Wnt)-signaling pathways, 10 which are believed to keep stem cells in a dedifferentiated and selfrenewal state. 11,12 Wnt signaling is an evolutionary conserved signal transduction cascade, transmitting signals through cell-cell contact and regulates cell fate, polarity, differentiation, migration and thereby organogenesis and fetal development.…”

Lung Pericytes and Resident Fibroblasts

“…2,3,6,9,10,12e16 Such broad adaptability is proposed to enable pericytes and resident fibroblasts to repeatedly adjust to support growing, injured, or regenerating vascular or airway structures. 2,6,13 Figure 1 Tissue architecture and mesenchymal lineages in the lung. A: Electron microscopy photomicrographs of normal mouse lung showing fibroblast processes abutting epithelium and pericyte processes attached to endothelium and within a loose capillary basement membrane.…”

“…5,6,18 The receptor, PDGFR-b, marks pericytes and establishes their interactions with endothelial cells. Endothelial cells produce its ligand PDGF-B when sprouting, to which the pericytes respond by proliferating and migrating to attach to and cover the growing vessel.…”

“…67 Pericytes expressing immune surveillance and effector genes may therefore function in roles traditionally envisioned for macrophages. 6,53,58,64,68 Indeed, most of the immunological genes and functions identified in pericytes were long since recognized and still most commonly studied in monocytes and macrophages. 10,23,53,58,62 Distinctions between resident tissue macrophages and macrophages differentiating from immigrating monocytes have recently become far better appreciated.…”