Teatime: epigallocatechin gallate targets fibroblast–epithelial cell crosstalk to combat lung fibrosis
Olivier Burgy, Melanie Königshoff
Olivier Burgy, Melanie Königshoff
Published September 17, 2024
Citation Information: J Clin Invest. 2024;134(18):e183970. https://doi.org/10.1172/JCI183970.
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Commentary

Teatime: epigallocatechin gallate targets fibroblast–epithelial cell crosstalk to combat lung fibrosis

Abstract

Epigallocatechin gallate (EGCG) is a polyphenol plant metabolite abundant in tea that has demonstrated antifibrotic properties in the lung. In this issue of the JCI, Cohen, Brumwell, and colleagues interrogated the mechanistic action of EGCG by investigating lung biopsies of patients with mild interstitial lung disease (ILD) who had undergone EGCG treatment. EGCG targeted the WNT inhibitor SFRP2, which was enriched in fibrotic fibroblasts and acted as a TGF-β target, with paracrine effects leading to pathologic basal metaplasia of alveolar epithelial type 2 cells. This study emphasizes the epithelial-mesenchymal trophic unit as a central signaling hub in lung fibrosis. Understanding and simultaneous targeting of interlinked signaling pathways, such as TGF-β and WNT, paves the road for future treatment options for pulmonary fibrosis.

Authors

Olivier Burgy, Melanie Königshoff

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Figure 1

TGF-β and WNT orchestrate mesenchymal-epithelium crosstalk to drive IPF.

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TGF-β and WNT orchestrate mesenchymal-epithelium crosstalk to drive IPF....
Activated fibroblasts produce components of the WNT signaling such as SFRPs and so-called noncanonical WNT ligands in response to TGF-β. TGF-β and WNT signals act on the epithelial compartment and promote an impaired communication within the epithelial-mesenchymal trophic unit. Immune cells may also secrete factors to contribute to alveolar epithelial cell reprogramming and basal metaplasia. A consequence of this vicious central signaling hub relies on the accumulation of basaloid and basal-like cells, which will line up often in close proximity to fibroblastic foci during late-stage IPF. Potential therapeutics, such as the EGCG polyphenol, that target both TGF-β and WNT signaling hold promise to redirect mesenchymal-epithelium dialog in the organization of tissue repair.