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

Authors
 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 
Citation
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol.24(22) : 13507-13522, 2020-10 
Journal Title
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 
ISSN
 1582-1838 
Issue Date
2020-10
Keywords
PTD-BMP-7 ; and peritoneal fibrosis ; protein transduction domain
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.
Files in This Item:
T202005244.pdf Download
DOI
10.1111/jcmm.15992
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180776
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