Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice.
Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice.
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DOI：
10.1093/ndt/gfab286
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发表时间：
2022-02-25
期刊：
影响因子：
--
通讯作者：
Kuwabara T
中科院分区：
文献类型：
--
作者：
Nishiguchi Y;Hata Y;Date R;Fujimoto D;Umemoto S;Kanki T;Yokoi H;Mori KP;Handa T;Watanabe-Takano H;Kanai Y;Yasoda A;Izumi Y;Kakizoe Y;Mochizuki N;Mukoyama M;Kuwabara T
骨素（Osteocrin，Osteocrin）是一种骨源性体液因子，通过增强利钠肽（natriuretic peptide，NP）系统作用于心脏和骨骼。卵巢癌基因多态性与肾功能下降有关，但其在肾脏中的病理生理作用尚不清楚。使用系统性Ostn敲除（KO）小鼠研究内源性Ostn的作用。作为Ostrin给药的模型，产生了与KO（KO-Tg）杂交的肝脏特异性Ostn过表达小鼠。对这些小鼠进行单侧缺血再灌注损伤（IRI），并评价损伤21天后的肾脏病变。使用聚合酶链反应（PCR）阵列对Wnt/β-连环蛋白通路进行全面分析。报告质粒转染的近端肾小管细胞（NRK 52 E）被用来研究ODN影响该途径的机制。损伤后，与野生型小鼠相比，KO小鼠显示出肾脏纤维化的边缘恶化，具有可比的肾脏萎缩。KO-Tg小鼠表现出显著改善的肾萎缩，纤维化和肾小管损伤，以及减少纤维化和炎症相关基因的表达。PCR阵列显示KO-Tg小鼠中Wnt/β-catenin途径的激活减弱。下游靶标Mmp 7、Myc和Axin 2显示出类似的结果。MMP 7和Wnt 2诱导皮质髓质近端小管损伤后，但没有在KO-Tg。在NRK 52 E中，ODN显著增强NP对转化生长因子β1诱导的Wnt/β-catenin通路激活的抑制作用，该通路由环磷酸鸟苷类似物复制。异位卵巢过度表达可改善缺血再灌注后的肾损伤。在急性肾脏疾病向慢性肾脏疾病转变的过程中，奥沙利铂可能代表可能的肾脏保护作用，因此可作为一种潜在的治疗策略。
Osteocrin (OSTN), a bone-derived humoral factor, was reported to act on heart and bone by potentiating the natriuretic peptide (NP) system. Ostn gene polymorphisms have been associated with renal function decline, but its pathophysiological role in the kidney remains unclear. The role of endogenous OSTN was investigated using systemic Ostn-knockout (KO) mice. As a model for OSTN administration, liver-specific Ostn-overexpressing mice crossed with KO (KO-Tg) were generated. These mice were subjected to unilateral ischemia–reperfusion injury (IRI) and renal lesions after 21 days of insult were evaluated. A comprehensive analysis of the Wnt/β-catenin pathway was performed using a polymerase chain reaction (PCR) array. Reporter plasmid-transfected proximal tubular cells (NRK52E) were used to investigate the mechanism by which OSTN affects the pathway. After injury, KO mice showed marginal worsening of renal fibrosis compared with wild-type mice, with comparable renal atrophy. KO-Tg mice showed significantly ameliorated renal atrophy, fibrosis and tubular injury, together with reduced expressions of fibrosis- and inflammation-related genes. The PCR array showed that the activation of the Wnt/β-catenin pathway was attenuated in KO-Tg mice. The downstream targets Mmp7, Myc and Axin2 showed similar results. MMP7 and Wnt2 were induced in corticomedullary proximal tubules after injury, but not in KO-Tg. In NRK52E, OSTN significantly potentiated the inhibitory effects of NP on transforming growth factor β1–induced activation of the Wnt/β-catenin pathway, which was reproduced by a cyclic guanosine monophosphate analog. Ectopic Ostn overexpression ameliorated subsequent renal injury following ischemia–reperfusion. OSTN could represent possible renoprotection in acute to chronic kidney disease transition, thus serving as a potential therapeutic strategy.
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影响因子：
5.7
作者：
Li N;Xi Y;Tinsley HN;Gurpinar E;Gary BD;Zhu B;Li Y;Chen X;Keeton AB;Abadi AH;Moyer MP;Grizzle WE;Chang WC;Clapper ML;Piazza GA
通讯作者：
Piazza GA
影响因子：
4.9
作者：
Kohzuki, M;Kamimoto, M;Yoshida, K
通讯作者：
Yoshida, K
影响因子：
4
作者：
Kita, Shunbun;Nishizawa, Hitoshi;Shimomura, Iichiro
通讯作者：
Shimomura, Iichiro
DOI：
10.1093/ehjcvp/pvv040
发表时间：
2016-04-01
影响因子：
7.1
作者：
Lee, Candace Y. W.;Huntley, Brenda K.;Burnett, John C., Jr.
通讯作者：
Burnett, John C., Jr.
影响因子：
13.2
作者：
Lewis, J;Salem, MM;Allgren, RL
通讯作者：
Allgren, RL