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Peer-reviewedCC BY 4.0PLOS One

Exogenous tryptophan aggravates experimental lung fibrosis through activation of AKT-mTORC1 pathway

  • Jisu Hong1
  • Yunha Nam1
  • Jib Yong Jung1
  • Jun Yeong Baek1
  • Eun Ji Park1
  • Yemin Choi1
  • Shinhee Park1
  • Ae-Rin Baek1
  • Hun-Gyu Hwang1
  • Junehyuk Lee1
  • An-Soo Jang1
  • Do-Jin Kim1
3 more authors
  • Su Sie Chin2
  • Woo Jin Kim3
  • Sung-Woo Park1
  1. 1Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
  2. 2Department of Pathology, Soonchunhyang University Bucheon Hospital, Gyeonggi-Do, South Korea
  3. 3Department of Internal Medicine Environmental Health Center, Kangwon National University, Chuncheon-si, Gangwon-do, South Korea
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Abstract

Idiopathic pulmonary fibrosis (IPF) is marked by aberrant lung remodeling and excessive extracellular matrix (ECM) accumulation. Previously, we observed elevated tryptophan (TRP) levels in the lungs of IPF patients, but its role in fibrogenesis remained unclear. This study examines whether TRP modulate the severity of lung fibrosis by measuring ECM component expression in TRP-treated lung fibroblasts. The activities of key TRP metabolism enzymes, tryptophan hydroxylase (TPH-1) and indoleamine 2,3-dioxygenase (IDO/TDO), were also assessed in IPF lung. Exogenous TRP administration in bleomycin-exposed mice significantly exacerbated lung damage and fibrosis. TPH-1 levels were elevated in lung tissues and primary fibroblasts of IPF patients compared to controls, while IDO/TDO expression showed no significant differences between two groups. TRP treatment increased fibroblast proliferation and upregulated collagen, fibronectin, and α-smooth muscle actin expression, whereas TRP deprivation reduced these ECM component levels. Additionally, TRP upregulated the AKT-mTORC1 and TGF-β1 signaling pathways in IPF fibroblasts. These findings indicate that elevated TRP levels contribute to IPF pathogenesis and suggest that targeting the TRP pathway could offer therapeutic potential for lung fibrosis including IPF.

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Cite

BibTeXRIS
BibTeX
@article{hong2026exogenous,
  title = {{Exogenous tryptophan aggravates experimental lung fibrosis through activation of AKT-mTORC1 pathway}},
  author = {Jisu Hong and Yunha Nam and Jib Yong Jung and Jun Yeong Baek and Eun Ji Park and Yemin Choi and Shinhee Park and Ae-Rin Baek and Hun-Gyu Hwang and Junehyuk Lee and An-Soo Jang and Do-Jin Kim and Su Sie Chin and Woo Jin Kim and Sung-Woo Park},
  journal = {PLOS One},
  year = {2026},
  month = nov,
  doi = {10.1371/journal.pone.0361463},
  url = {https://doi.org/10.1371/journal.pone.0361463},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Exogenous tryptophan aggravates experimental lung fibrosis through activation of AKT-mTORC1 pathway
AU  - Jisu Hong
AU  - Yunha Nam
AU  - Jib Yong Jung
AU  - Jun Yeong Baek
AU  - Eun Ji Park
AU  - Yemin Choi
AU  - Shinhee Park
AU  - Ae-Rin Baek
AU  - Hun-Gyu Hwang
AU  - Junehyuk Lee
AU  - An-Soo Jang
AU  - Do-Jin Kim
AU  - Su Sie Chin
AU  - Woo Jin Kim
AU  - Sung-Woo Park
PY  - 2026
DA  - 2026/11/03
JO  - PLOS One
DO  - 10.1371/journal.pone.0361463
UR  - https://doi.org/10.1371/journal.pone.0361463
AB  - Idiopathic pulmonary fibrosis (IPF) is marked by aberrant lung remodeling and excessive extracellular matrix (ECM) accumulation. Previously, we observed elevated tryptophan (TRP) levels in the lungs of IPF patients, but its role in fibrogenesis remained unclear. This study examines whether TRP modulate the severity of lung fibrosis by measuring ECM component expression in TRP-treated lung fibroblasts. The activities of key TRP metabolism enzymes, tryptophan hydroxylase (TPH-1) and indoleamine 2,3-dioxygenase (IDO/TDO), were also assessed in IPF lung. Exogenous TRP administration in bleomycin-exposed mice significantly exacerbated lung damage and fibrosis. TPH-1 levels were elevated in lung tissues and primary fibroblasts of IPF patients compared to controls, while IDO/TDO expression showed no significant differences between two groups. TRP treatment increased fibroblast proliferation and upregulated collagen, fibronectin, and α-smooth muscle actin expression, whereas TRP deprivation reduced these ECM component levels. Additionally, TRP upregulated the AKT-mTORC1 and TGF-β1 signaling pathways in IPF fibroblasts. These findings indicate that elevated TRP levels contribute to IPF pathogenesis and suggest that targeting the TRP pathway could offer therapeutic potential for lung fibrosis including IPF.
SN  - 1932-6203
ER  -