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珍しい中型ティラノサウルス類の骨?…北海道 (読売新聞)

北海道大学は20日、北海道芦別市の白亜紀後期(約1億年~約6600万年前)の地層から見つかった恐竜の化石が、ティラノサウルス類の尾の骨である可能性が高いことが分...

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A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy.

著者 Guan Y , Nakano D , Zhang Y , Li L , Liu W , Nishida M , Kuwabara T , Morishita A , Hitomi H , Mori K , Mukoyama M , Masaki T , Hirano K , Nishiyama A
J Pharmacol Sci.2017 Sep 14 ; ():.
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The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump. PAR-1 expression was increased in glomeruli of mice treated with doxorubicin. Q94 treatment significantly suppressed the increased albuminuria in these nephropathic mice. Pathological analysis showed that Q94 treatment significantly attenuated periodic acid-Schiff and desmin staining, indicators of podocyte injury, and also decreased glomerular levels of podocin and nephrin. Furthermore, thrombin increased intracellular calcium levels in podocytes. This increase was suppressed by Q94 and Rox4560, a transient receptor potential cation channel (TRPC)3/6 antagonist. In addition, both Q94 and Rox4560 suppressed the doxorubicin-induced increase in activities of caspase-9 and caspase-3 in podocytes. These data suggested that PAR-1 contributes to development of podocyte and glomerular injury and that PAR-1 antagonists have therapeutic potential.
PMID: 29110957 [PubMed - as supplied by publisher]
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