Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic mice
Encapsulating peritoneal sclerosis is one of the most serious complications of long-term peritoneal dialysis. The pathogenesis of encapsulating peritoneal sclerosis has not been elucidated, but several putative factors necessary for the development of peritoneum fibrosis (PF) have been reported. How...
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Japanese Association for Laboratory Animal Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637371/ |
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pubmed-46373712015-11-09 Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic mice Yoh, Keigyou Ojima, Masami Takahashi, Satoru Original Encapsulating peritoneal sclerosis is one of the most serious complications of long-term peritoneal dialysis. The pathogenesis of encapsulating peritoneal sclerosis has not been elucidated, but several putative factors necessary for the development of peritoneum fibrosis (PF) have been reported. However, the roles of T helper (Th) cells in the progression of PF are unknown. The purpose of this study was to clarify the roles of Th1, Th2, and Th17 cells in the progression of PF. T-bet, GATA-3, and RORγt are Th1, Th2, and Th17 lineage commitment transcription factors, respectively. We previously generated Th1-biased (T-bet transgenic (Tg)) mice, Th2-biased (GATA-3 Tg) mice, and Th17-biased (RORγt Tg) mice. In this study, Th1, Th2, Th17-biased, and wild-type mice were administered chlorhexidine gluconate (CG) intraperitoneally and analyzed on day 21. CG-injected GATA-3 Tg mice showed a distended intestinal tract and developed marked thickening of the submesothelial space compared with the other groups. CG-injected GATA-3 Tg mice also showed significant expression of α-SMA positive cells, macrophages, and collagen III in the submesothelium. In contrast, CG-injected T-bet Tg mice only developed mild peritoneal fibrosis. Cytokines analysis in peritoneal fluid showed that IFN-γ was significantly increased in CG-injected T-bet Tg mice and that IL-13 was significantly increased in CG-injected GATA-3 Tg mice. Moreover, intraperitoneal administration of IFN-γ improved PF in GC-injected wild-type mice. Our results suggest that Th2 cells may play roles in the development of experimental PF and that Th1 cells may alleviate the severity of experimental PF. Japanese Association for Laboratory Animal Science 2015-07-09 2015 /pmc/articles/PMC4637371/ /pubmed/26156402 http://dx.doi.org/10.1538/expanim.15-0019 Text en ©2015 Japanese Association for Laboratory Animal Science http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Yoh, Keigyou Ojima, Masami Takahashi, Satoru |
| spellingShingle |
Yoh, Keigyou Ojima, Masami Takahashi, Satoru Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic mice |
| author_facet |
Yoh, Keigyou Ojima, Masami Takahashi, Satoru |
| author_sort |
Yoh, Keigyou |
| title |
Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal
fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic
mice |
| title_short |
Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal
fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic
mice |
| title_full |
Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal
fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic
mice |
| title_fullStr |
Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal
fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic
mice |
| title_full_unstemmed |
Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal
fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic
mice |
| title_sort |
th2-biased gata-3 transgenic mice developed severe experimental peritoneal
fibrosis compared with th1-biased t-bet and th17-biased rorγt transgenic
mice |
| description |
Encapsulating peritoneal sclerosis is one of the most serious complications of long-term
peritoneal dialysis. The pathogenesis of encapsulating peritoneal sclerosis has not been
elucidated, but several putative factors necessary for the development of peritoneum
fibrosis (PF) have been reported. However, the roles of T helper (Th) cells in the
progression of PF are unknown. The purpose of this study was to clarify the roles of Th1,
Th2, and Th17 cells in the progression of PF. T-bet, GATA-3, and RORγt are Th1, Th2, and
Th17 lineage commitment transcription factors, respectively. We previously generated
Th1-biased (T-bet transgenic (Tg)) mice, Th2-biased (GATA-3 Tg) mice, and Th17-biased
(RORγt Tg) mice. In this study, Th1, Th2, Th17-biased, and wild-type mice were
administered chlorhexidine gluconate (CG) intraperitoneally and analyzed on day 21.
CG-injected GATA-3 Tg mice showed a distended intestinal tract and developed marked
thickening of the submesothelial space compared with the other groups. CG-injected GATA-3
Tg mice also showed significant expression of α-SMA positive cells, macrophages, and
collagen III in the submesothelium. In contrast, CG-injected T-bet Tg mice only developed
mild peritoneal fibrosis. Cytokines analysis in peritoneal fluid showed that IFN-γ was
significantly increased in CG-injected T-bet Tg mice and that IL-13 was significantly
increased in CG-injected GATA-3 Tg mice. Moreover, intraperitoneal administration of IFN-γ
improved PF in GC-injected wild-type mice. Our results suggest that Th2 cells may play
roles in the development of experimental PF and that Th1 cells may alleviate the severity
of experimental PF. |
| publisher |
Japanese Association for Laboratory Animal Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637371/ |
| _version_ |
1613498958180515840 |