Institution
Kanazawa Medical University
Education•Kanazawa, Japan•
About: Kanazawa Medical University is a education organization based out in Kanazawa, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 3103 authors who have published 6322 publications receiving 144592 citations. The organization is also known as: Kanazawa ika daigaku.
Topics: Population, Cancer, Diabetes mellitus, Lung cancer, Blood pressure
Papers published on a yearly basis
Papers
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TL;DR: Results indicated that laminin and fibronectin may promote the growth of axons in biodegradable collagen grafts, which guided nerve regeneration well and allowed the formation of epineurium.
137 citations
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TL;DR: Fenofibrate can attenuate lipotoxicity-induced glomerular and tubulointerstitial injuries, with enhancement of renal lipolysis, and whether amelioration of renallipotoxicity by PPARα agonists will turn out to be a useful strategy against CKD will require direct testing.
137 citations
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TL;DR: The results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation.
135 citations
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TL;DR: A model that perturbed gap-filling synthesis following dual incision in NER generates single-strand DNA gaps and hence initiates H2AX phosphorylation by ATR with the aid of RPA and ATRIP is proposed.
Abstract: Human histone H2AX is rapidly phosphorylated on serine 139 in response to DNA double-strand breaks and plays a crucial role in tethering the factors involved in DNA repair and damage signaling. Replication stress caused by hydroxyurea or UV also initiates H2AX phosphorylation in S-phase cells, although UV-induced H2AX phosphorylation in non-cycling cells has recently been observed. Here we study the UV-induced H2AX phosphorylation in human primary fibroblasts under growth-arrested conditions. This reaction absolutely depends on nucleotide excision repair (NER) and is mechanistically distinct from the replication stress-induced phosphorylation. The treatment of cytosine-beta-D-arabinofuranoside strikingly enhances the NER-dependent H2AX phosphorylation and induces the accumulation of replication protein A (RPA) and ATR-interacting protein (ATRIP) at locally UV-damaged subnuclear regions. Consistently, the phosphorylation appears to be mainly mediated by ataxia-telangiectasia mutated and Rad3-related (ATR), although Chk1 (Ser345) is not phosphorylated by the activated ATR. The cellular levels of DNA polymerases delta and epsilon and proliferating cell nuclear antigen are markedly reduced in quiescent cells. We propose a model that perturbed gap-filling synthesis following dual incision in NER generates single-strand DNA gaps and hence initiates H2AX phosphorylation by ATR with the aid of RPA and ATRIP.
135 citations
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TL;DR: Defective autophagy in IECs may predispose to CD ileitis via impaired clearance of IRE1&agr; aggregates during ER stress at this site, which aggravates dextran sodium sulfate–induced colitis.
Abstract: ATG16L1T300A, a major risk polymorphism in Crohn's disease (CD), causes impaired autophagy, but it has remained unclear how this predisposes to CD. In this study, we report that mice with Atg16l1 deletion in intestinal epithelial cells (IECs) spontaneously develop transmural ileitis phenocopying ileal CD in an age-dependent manner, driven by the endoplasmic reticulum (ER) stress sensor IRE1α. IRE1α accumulates in Paneth cells of Atg16l1ΔIEC mice, and humans homozygous for ATG16L1T300A exhibit a corresponding increase of IRE1α in intestinal epithelial crypts. In contrast to a protective role of the IRE1β isoform, hyperactivated IRE1α also drives a similar ileitis developing earlier in life in Atg16l1;Xbp1ΔIEC mice, in which ER stress is induced by deletion of the unfolded protein response transcription factor XBP1. The selective autophagy receptor optineurin interacts with IRE1α, and optineurin deficiency amplifies IRE1α levels during ER stress. Furthermore, although dysbiosis of the ileal microbiota is present in Atg16l1;Xbp1ΔIEC mice as predicted from impaired Paneth cell antimicrobial function, such structural alteration of the microbiota does not trigger ileitis but, rather, aggravates dextran sodium sulfate-induced colitis. Hence, we conclude that defective autophagy in IECs may predispose to CD ileitis via impaired clearance of IRE1α aggregates during ER stress at this site.
135 citations
Authors
Showing all 3113 results
Name | H-index | Papers | Citations |
---|---|---|---|
Michael Marmot | 193 | 1147 | 170338 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Zena Werb | 168 | 473 | 122629 |
Toshio Hirano | 120 | 401 | 55721 |
John T. Isaacs | 88 | 356 | 28217 |
Hiroshi Sasaki | 76 | 644 | 24222 |
Takuji Tanaka | 75 | 490 | 20946 |
Hiroshi Shimizu | 71 | 1368 | 26668 |
Daisuke Koya | 67 | 294 | 18746 |
Masashi Tanaka | 65 | 396 | 17110 |
Masashi Akiyama | 65 | 685 | 16404 |
Masayoshi Takeuchi | 64 | 279 | 13651 |
Takashi Yoshida | 63 | 328 | 13680 |
Tsutomu Hatano | 61 | 299 | 13668 |