We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-β1 (TGFβ1) receptor kinase that when given orally to patients with idiopathic pulmonary fibrosis (IPF) reversed profibrotic biomarkers in their diagnostic biopsies. Here, we extend these findings to advanced pulmonary fibrosis using cultured precision-cut lung slices from explants of patients with IPF undergoing transplantation. During these experiments, we were surprised to discover that not only did EGCG attenuate TGFβ1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.
- interstitial fibrosis
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YW and HAC are joint senior authors.
Contributors YW and HAC made contributions to conception and design of the work and interpretation of data. YW, WD, T-CH, AB, JJ, MLC, and CJLS acquired, analysed and interpreted data. XL, JK-T and PJW provided critical experimental specimens. YW and HAC wrote the manuscript. All authors approved the final version.
Funding This work has been funded by Three Lakes Foundation (HAC), NIH R01 HL142265 and R35 HL150767 (HAC) and R21 AG052744 (CJLS).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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