Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model.
Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model.
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DOI：
10.1186/s12876-015-0269-3
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发表时间：
2015-04-01
影响因子：
2.4
通讯作者：
Nakajima A
中科院分区：
文献类型：
--
作者：
Nozaki Y;Fujita K;Wada K;Yoneda M;Kessoku T;Shinohara Y;Imajo K;Ogawa Y;Nakamuta M;Saito S;Masaki N;Nagashima Y;Terauchi Y;Nakajima A
尽管许多与非酒精性脂肪性肝炎（NASH）密切相关的因素和分子已被报道，但诱导型一氧化氮合酶（iNOS）衍生的一氧化氮（NO）在NASH进展中的作用仍不清楚。因此，我们利用高脂饮食（HFD）条件下的系统性inos敲除小鼠，通过长期随访研究了inos来源的NO在NASH发病机制中的作用。inos敲除小鼠和野生型小鼠分别饲喂基础或HFD 10周或48周。评估脂质积累、纤维化和炎症，并分析与NASH密切相关的各种因素和分子。48周HFD后，与野生型小鼠相比，inos基因敲除小鼠的肝脏中观察到明显的纤维化和炎症（NASH的指标）；然而，与野生型相比，inos敲除小鼠肝脏中的脂质积累较少。在HFD条件下，观察到inos缺陷小鼠肝脏中受NF-kB转录控制的各种细胞因子的表达增加。inos来源的NO可能通过防止Kupffer细胞中NF-kB活化介导的纤维化和炎症，在HFD期间对NASH进展起保护作用。缺乏inos衍生的NO会加速向NASH的进展，而不会产生过多的脂质积累。
Although many of the factors and molecules closely associated with non-alcoholic steatohepatitis (NASH) have been reported, the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) on the progression of NASH remains unclear. We therefore investigated the role of iNOS-derived NO in NASH pathogenesis with a long-term follow-up study using systemic iNOS-knockout mice under high-fat diet (HFD) conditions. iNOS-knockout and wild-type mice were fed a basal or HFD for 10 or 48 weeks. Lipid accumulation, fibrosis, and inflammation were evaluated, and various factors and molecules closely associated with NASH were analyzed. Marked fibrosis and inflammation (indicators of NASH) were observed in the livers of iNOS-knockout mice compared to wild-type mice after 48 weeks of a HFD; however, lipid accumulation in iNOS-knockout mice livers was less than in the wild-type. Increased expressions of various cytokines that are transcriptionally controlled by NF-kB in iNOS-deficient mice livers were observed during HFD conditions. iNOS-derived NO may play a protective role against the progression to NASH during an HFD by preventing fibrosis and inflammation, which are mediated by NF-kB activation in Kupffer cells. A lack of iNOS-derived NO accelerates progression to NASH without excessive lipid accumulation.
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影响因子：
13.5
作者：
Fujita, Koji;Nozaki, Yuichi;Nakajima, Atsushi
通讯作者：
Nakajima, Atsushi
影响因子：
3.9
作者：
Cha, Hye-Na;Kim, Yong-Woon;Park, So-Young
通讯作者：
Park, So-Young
影响因子：
82.9
作者：
Perreault, M;Marette, A
通讯作者：
Marette, A
影响因子：
25.7
作者：
Nozaki, Yuichi;Fujita, Koji;Nakajima, Atsushi
通讯作者：
Nakajima, Atsushi
超越胰岛素抵抗：非酒精性脂肪性肝炎的先天免疫力。
影响因子：
13.5
作者：
Maher, Jacquelyn J.;Leon, Pablo;Ryan, James C.
通讯作者：
Ryan, James C.