Ono, Hiroyuki Tokushima University Tokushima University Educator and Researcher Directory
Abe, Hideharu Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Sakurai, Akiko Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Ochi, Arisa Tokushima University
Tominaga, Tatsuya Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tamaki, Masanori Tokushima University Tokushima University Educator and Researcher Directory
Nagai, Kojiro Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kohashi, Masayuki Otsuka Pharmaceutical. Co. Ltd.
Doi, Toshio Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Thesis or Dissertation
Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality compared with other causes of renal diseases. We previously found that Smad1 plays a critical role in the development of DN both in vitro and in vivo. However, functional interaction between Smad1 and Smad3 signaling in DN is unclear. Here, we addressed the molecular interplay between Smad1 and Smad3 signaling under a diabetic condition by using Smad3-knockout diabetic mice. Extracellular matrix (ECM) protein overexpression and Smad1 activation were observed in the glomeruli of db/db mice but were suppressed in the glomeruli of Smad3+/−; db/db mice. Smad3 activation enhanced the phosphorylation of Smad1 C-terminal domain but decreased the phosphorylation of linker domain, thus regulating Smad1 activation in advanced glycation end product-treated mesangial cells (MCs). However, forced phosphorylation of the Smad1 linker domain did not affect Smad3 activation in MCs. Phosphorylation of the Smad1 linker domain increased in Smad3+/−; db/db mice and probucol-treated db/db mice, which was consistent with the attenuation of ECM overproduction. These results indicate that Smad3 expression and activation or probucol treatment alters Smad1 phosphorylation, thus suggesting new molecular mechanisms underlying DN development and progression.
本論文は, 著者Hiroyuki Onoの学位論文として提出され, 学位審査・授与の対象となっている。
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|DOI (Published Version)|
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k3216_abstract_review.pdf 263 KB
k3216_fulltext.pdf 2.54 MB
|MEXT report number||
Doctor of Medical Science