Newly designed Protein Transduction Domain (PTD)-mediated BMP-7 is a potential therapeutic for peritoneal fibrosis

Seonghun Kim, Dong Ho Shin, Bo Young Nam, Hye Young Kang, Jimin Park, Meiyan Wu, Nam Hee Kim, Hyun Sil Kim, Jung Tak Park, Seung Hyeok Han, Shin Wook Kang, Jong In Yook, Tae Hyun Yoo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

While the bone morphogenetic protein-7 (BMP-7) is a well-known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half-life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein-7 (BMP-7). This study aims at evaluating the therapeutic effects of PTD-BMP-7 consisted of PTD and full-length BMP-7 on epithelial-mesenchymal transition (EMT)-related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF-β1 or TGF-β1 + PTD-BMP-7. Peritoneal dialysis (PD) catheters were inserted into Sprague-Dawley rats, and these rats were infused intra-peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD-BMP-7. In vitro, TGF-β1 treatment significantly increased fibronectin, type I collagen, α-SMA and Snail expression, while reducing E-cadherin expression in HPMCs (P <.001). PTD-BMP-7 treatment ameliorated TGF-β1-induced fibronectin, type I collagen, α-SMA and Snail expression, and restored E-cadherin expression in HPMCs (P <.001). In vivo, the expressions of EMT-related molecules and the thickness of the sub-mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra-peritoneal administration of PTD-BMP-7. PTD-BMP-7 treatment significantly inhibited the progression of established PD fibrosis. These findings suggest that PTD-BMP-7, as a prodrug of BMP-7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.

Original languageEnglish
Pages (from-to)13507-13522
Number of pages16
JournalJournal of Cellular and Molecular Medicine
Volume24
Issue number22
DOIs
Publication statusPublished - 2020 Nov

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF‐2014R1A2A1A11050098, NRF‐2017R1A2B4005720, NRF‐2019R1A2C2084535) funded by the Korea government (MSIP), a grant from the National Research Foundation of Korea (NRF‐2020R1I1A1A01072977) funded by the Korea government (MOE), a grant from the Korean Health Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI14C2003000016).

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF-2014R1A2A1A11050098, NRF-2017R1A2B4005720, NRF-2019R1A2C2084535) funded by the Korea government (MSIP), a grant from the National Research Foundation of Korea (NRF-2020R1I1A1A01072977) funded by the Korea government (MOE), a grant from the Korean Health Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI14C2003000016).

Publisher Copyright:
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

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