Resolvin D1 stimulates epithelial wound repair and inhibits TGF-β induced EMT whilst reducing fibroproliferation and collagen production

Shenxing Zheng, Qian Wang, Vijay D'Souza, Domokos Bartis, Rachel Dancer, Dhruv Parekh, Fang Gao Smith, Qingquan Lian, Shengwei Jin, David Thickett

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19 Citations (Scopus)
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Acute and chronic inflammatory lung diseases are often associated with epithelial cell injury/loss and fibroproliferative responses. ResolvinD1 (RvD1) is biosynthesized during the resolution phase of inflammatory response and exerts potent anti-inflammatory and promotes resolution of inflammatory lung diseases. The aim of this study was to investigate whether RvD1 exerts protective effects on alveolar epithelial cell function / differentiation and protects against fibroproliferative stimuli. Primary human alveolar type II cells were used to model the effects of RvD1 in vitro upon wound repair, proliferation, apoptosis, transdifferentiation and epithelial mesenchymal transition (EMT). Effects of RvD1 upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also examined. RvD1 promoted alveolar type II (ATII) cell wound repair and proliferation. RvD1 protected ATII cells against sFas-ligand/TNF-α-induced apoptosis and inhibition on cell proliferation and viability. RvD1 promoted ATII cells transdifferentiation. Moreover, we demonstrate that RvD1 inhibited EMT in response to TGF-β. Furthermore RvD1 inhibited HLF proliferation, collagen production and myofibroblast differentiation induced by both TGF-β and bronchoalveolar lavage fluid (BALF) from ARDS patients. The effects of RvD1 were PI3-kinase dependent and mediated via the resolvin receptor. RvD1 seems to promote alveolar epithelial repair by stimulating ATII cells wound repair, proliferation, reducing apoptosis and inhibiting TGF-β induced EMT. While RvD1 reduced fibroproliferation, collagen production and myofibroblast differentiation. Together, these results suggest a potential new therapeutic strategy for preventing and treating chronic diseases (such as IPF) as well as the fibroproliferative phase of ARDS by targeting RvD1 actions that emphasizes natural resolution signalling pathways.
Original languageEnglish
JournalLaboratory investigation
Publication statusPublished - 30 Oct 2017


  • alveolar type II cells
  • lung fibroblast
  • Idiopathic Pulmonary Fibrosis
  • acute respiratory distress syndrome
  • resolvins

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • General Medicine


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