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title alternative
間葉系幹細胞は炎症抑制およびTGF-β1シグナルの抑制を介し腹膜線維化を改善させる
creator
subject
epithelial-to-mesenchymal transition
hepatocyte growth factor
mesenchymal stem cells
peritoneal fibrosis
transforming growth factor-β1
NDC
Medical sciences
abstract
Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have regenerative capability and exert paracrine actions on damaged tissues. Since peritoneal fibrosis is a serious complication of peritoneal dialysis, we tested whether MSCs suppress this using a chlorhexidine gluconate model in rats. Although MSCs isolated from green fluorescent protein? positive rats were detected for only 3 days following their injection, immunohistochemical staining showed that MSCs suppressed the expression of mesenchymal cells, their effects on the deposition of extracellular matrix proteins, and the infiltration of macrophages for 14 days. Moreover, MSCs reduced the functional impairment of the peritoneal membrane. Cocultures of MSCs and human peritoneal mesothelial cells using a Transwell system indicated that the beneficial effects of MSCs on the glucose-induced upregulation of transforming growth factor-β1(TGF-β1) and fibronectin mRNA expression in the human cells were likely due to paracrine actions. Preincubation in MSC-conditioned medium suppressed TGFβ1- induced epithelial-to-mesenchymal transition, a-smooth muscle actin, and the decrease in zonula occludens-1 in cultured human peritoneal mesothelial cells. Although bone morphogenic protein 7 was not detected, MSCs secreted hepatocyte growth factor and a neutralizing antibody to this inhibited TGF-β1 signaling. Thus, our findings imply that MSCs ameliorate experimental peritoneal fibrosis by suppressing inflammation and TGF-β1 signaling in a paracrine manner.
date of created
2014-11-21
language
eng
nii type
Thesis or Dissertation
HU type
Doctoral Theses
DCMI type
text
format
application/pdf
text version
ETD
rights
Copyright(c) by Author
relation references
Toshinori Ueno, Ayumu Nakashima, Shigehiro Doi, Takeshi Kawamoto, Kiyomasa Honda, Yukio Yokoyama, Toshiki Doi, Yukihito Higashi, Noriaki Yorioka, Yukio Kato, Nobuoki Kohno and Takao Masaki; Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 signaling; Kidney International (2013) 84, 297-307, published online 13 March 2013 (doi: 10.1038/ki.2013.81)
relation references URL
http://dx.doi.org/10.1038/ki.2013.81
grantid
甲第6191号
degreeGrantor
広島大学(Hiroshima University)
degreename Ja
博士(医学)
degreename En
Philosophy in Medical Science
degreelevel
doctoral
date of granted
2013-05-23
department
Graduate School of Biomedical Science