Recent developments in the pathobiology of lung myofibroblasts

ABSTRACT

Introduction

Myofibroblasts are the primary executor and influencer in lung fibrosis. Latest studies on lung myofibroblast pathobiology have significantly advanced the understanding of the pathogenesis of lung fibrosis and shed new light on strategies targeting these cells to treat this disease.

Areas covered

This article reviewed the most recent progresses, mainly within the last 5 years, on the definition, origin, activity regulation, and targeting of lung myofibroblasts in lung fibrosis. We did a literature search on PubMed using the keywords below from the dates 2010 to 2020.

Expert opinion

With the improved cell lineage characterization and the advent of scRNA-seq, the field is having much better picture of the lung myofibroblast origin and mesenchymal heterogeneity. Additionally, cellular metabolism has emerged as a key regulation of lung myofibroblast pathogenic phenotype and is a promising therapeutic target for treating a variety of lung fibrotic disorders.

KEYWORDS:

• Lung fibrosis
• myofibroblast
• α-SMA
• cellular metabolism
• glycolysis
• glutaminolysis
• senescence
• apoptosis
• resolution

Article highlights

• It is time to redefine lung myofibroblasts.

• Lung myofibroblasts are originated from lung mesenchymal cells (Figure 1).

• Cellular metabolism, including glycolysis, de novo glycine, and proline synthesis, glutaminolysis, plays a key role in lung myofibroblast activation (Figure 2).

• Targeting lung myofibroblasts likely represents the best strategy to treat pulmonary fibrosis.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by NIH grant HL135830, Department of Defense grant W81XWH-20-1-0226, National Natural Science Foundation of China grants 81700067 and 81870056.