2. Academic Validation
  3. Induced pluripotent stem cell-derived conditioned medium, as well as nintedanib, ameliorates bleomycin-induced pulmonary fibrosis via suppressing endothelial-mesenchymal transition

Induced pluripotent stem cell-derived conditioned medium, as well as nintedanib, ameliorates bleomycin-induced pulmonary fibrosis via suppressing endothelial-mesenchymal transition

  • Respir Investig. 2025 Sep;63(5):904-914. doi: 10.1016/j.resinv.2025.07.005.
Wen-Kuang Yu 1,  Yi-Ping Yang 2,  Wei-Chih Chen 1,  Hsiao-Chin Shen 3,  Shih-Hwa Chiou 4,  Yu-Ling Ko 5,  Chuan-Yen Sun 1,  Vincent Yi-Fong Su 6,  Kuang-Yao Yang 7
Affiliations

Affiliations

  • 1 Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 2 Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 3 Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Evidence-based Medicine, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Microbiology and Immunology, School of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 4 Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; Genomic Research Center, Academia Sinica, Taipei, Taiwan.
  • 5 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 6 School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan.
  • 7 Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: kyyang@vghtpe.gov.tw.
PMID: 40683174 DOI: 10.1016/j.resinv.2025.07.005
Abstract

Background: Pulmonary fibrosis (PF), a debilitating lung disease, is heavily influenced by fibroblasts, which may arise from pulmonary endothelial cells through a process called endothelial-mesenchymal transition (EndoMT). While nintedanib and induced pluripotent stem cell-derived conditioned medium (iPSC-CM) have shown promise in PF treatment, their ability to suppress EndoMT remains uncertain.

Methods: PF was induced in C57BL/6 mice via intratracheal bleomycin (BLM) instillation. Nintedanib was administered orally, and iPSC-CM was injected through the tail vein. Concurrently, human pulmonary microvascular endothelial cells (HPMECs) were cultured with nintedanib and iPSC-CM, either individually or in combination, and then exposed to BLM to assess their ability to inhibit EndoMT in vitro.

Results: Masson's trichrome staining revealed substantial Collagen accumulation in the lungs of BLM-treated mice, which was significantly reduced by nintedanib and iPSC-CM, both individually and in combination, suggesting a reduction in PF. Immunohistochemistry staining and Western blot analysis showed that BLM stimulation increased the expression of collagen-1, α-SMA, and vimentin, while reducing VE-cadherin levels-effects that were reversed by treatment with nintedanib and iPSC-CM, either alone or in combination. Similarly, immunofluorescence staining and Western blotting of BLM-stimulated HPMECs indicated heightened EndoMT, which was effectively suppressed by nintedanib or iPSC-CM. Additionally, in both in vivo and in vitro BLM-induced EndoMT models, focal adhesion kinase (FAK) activity-a key driver of EndoMT-was significantly elevated. Treatment with nintedanib and iPSC-CM, either alone or in combination, markedly reduced FAK activation.

Conclusions: Nintedanib and iPSC-CM, whether used separately or together, effectively inhibited EndoMT and mitigated BLM-induced PF by suppressing FAK activity.

Keywords

Endothelial-mesenchymal transition; Focal adhesion kinase; Induced pluripotent stem cell-derived conditioned medium; Nintedanib; Pulmonary fibrosis.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z