Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways

Abstract

Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma.Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13.Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13.Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis.

Periostin—An inducer of pro-fibrotic phenotype in monocytes and monocyte-derived macrophages in systemic sclerosis

“…Our results support previous findings suggesting periostin as an important factor in recruiting macrophages in the tumor microenvironment [ 25 , 26 ]. It has also been reported that periostin plays an important role in inducing pericyte migration in the context of tissue fibrosis [ 27 ]. Taken together, these findings indicate that periostin may be involved in the promotion of various cell migrations.…”

Periostin increased by mechanical stress upregulates interleukin‐6 expression in the ligamentum flavum

“…It is found in various tissues involved in mechanical stress conditions, such as the periosteum, ligaments, blood vessels, heart, lungs, and the skin. Furthermore, periostin is recognized as an important molecule in various diseases, such as fibrosis in asthma, 29 scleroderma, 30 scar formation in myocardial infarction, 31 and migration of cancer cells. 32 Interestingly, the present study revealed that periostin is upregulated with mechanical stress in LF cells and also highly expressed in hypertrophied LF tissues, suggesting that it may be involved in the pathogenesis of LF hypertrophy.…”

Pericytes: The lung-forgotten cell type

“…Frontiers in Physiology frontiersin.org studies have suggested that, in vivo, cinnamaldehyde can reduce both IL-13-dependent and TGF-β-dependent periostin expression (Mitamura et al, 2018). It has also been shown that cinnamaldehyde mitigates increased pericyte migration caused by periostin as well as reducing IL-13-induced production of periostin by pericytes (Bignold and Johnson, 2021). This shows that important investigation into the use of periostin as a target for pharmacological intervention is underway and may yield useful drugs to treat fibrotic lung diseases in the future.…”