PARK7 deficiency inhibits fatty acid β-oxidation via PTEN to delay liver regeneration after hepatectomy.
PARK7 deficiency inhibits fatty acid β-oxidation via PTEN to delay liver regeneration after hepatectomy.
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PARK7 缺乏通过 PTEN 抑制脂肪酸 β 氧化，以延缓小鼠肝切除术后的肝脏再生。
DOI：
10.1002/ctm2.1061
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发表时间：
2022-09
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
短暂性再生相关性脂肪变性（TRAS）是一种暂时性肝脏脂质蓄积的过程，通过提供脂肪酸β-氧化产生的能量对肝脏再生至关重要，但TRAS的调控机制尚不清楚。帕金森综合征相关的deglycase（Park 7）/Dj 1是参与各种肝脏疾病的重要调节因子。在高脂饮食诱导的非酒精性脂肪肝小鼠中，Park 7缺乏改善了肝脂肪变性，但其在肝再生中的作用仍然未知Park 7敲除（公园7 −/−），肝细胞特异性Park 7基因敲除对Park 7 △hep和肝细胞特异性Park 7 ‐Pten双敲除小鼠进行2/3部分肝切除术（PHx）在PHx后36和48 h，在小鼠再生肝脏中观察到PARK 7表达增加。Park 7 −/−和Park 7 △hep小鼠在PHx后表现出延迟的肝再生和增强的TRAS。β氧化的关键调节因子PPARa和β氧化的限速酶肉毒碱棕榈酰转移酶1a（CPT 1a）在Park 7 △hep小鼠再生肝脏中的表达大幅降低。在Park 7 △hep小鼠的肝脏中观察到磷酸酶和张力蛋白同源物（PTEN）表达增加，这可能导致这些小鼠中延迟的肝再生，因为基因组缺失或药物抑制PTEN通过逆转PPARa和CPT 1a的下调而恢复了延迟的肝再生，从而加速了Park 7 △hep小鼠Park 7/Dj 1是一种新的PTEN依赖性脂肪酸β-氧化的调节剂，增加Park 7的表达可能是促进肝再生的一种有前途的策略。
Transient regeneration–associated steatosis (TRAS) is a process of temporary hepatic lipid accumulation and is essential for liver regeneration by providing energy generated from fatty acid β‐oxidation, but the regulatory mechanism underlying TRAS remains unknown. Parkinsonism‐associated deglycase (Park7)/Dj1 is an important regulator involved in various liver diseases. In nonalcoholic fatty liver diseased mice, induced by a high‐fat diet, Park7 deficiency improves hepatic steatosis, but its role in liver regeneration remains unknown Park7 knockout (Park7 −/−), hepatocyte‐specific Park7 knockout (Park7 △hep) and hepatocyte‐specific Park7‐Pten double knockout mice were subjected to 2/3 partial hepatectomy (PHx) Increased PARK7 expression was observed in the regenerating liver of mice at 36 and 48 h after PHx. Park7 −/− and Park7 △hep mice showed delayed liver regeneration and enhanced TRAS after PHx. PPARa, a key regulator of β‐oxidation, and carnitine palmitoyltransferase 1a (CPT1a), a rate‐limiting enzyme of β‐oxidation, had substantially decreased expression in the regenerating liver of Park7 △hep mice. Increased phosphatase and tensin homolog (PTEN) expression was observed in the liver of Park7 △hep mice, which might contribute to delayed liver regeneration in these mice because genomic depletion or pharmacological inhibition of PTEN restored the delayed liver regeneration by reversing the downregulation of PPARa and CPT1a and in turn accelerating the utilization of TRAS in the regenerating liver of Park7 △hep mice Park7/Dj1 is a novel regulator of PTEN‐dependent fatty acid β‐oxidation, and increasing Park7 expression might be a promising strategy to promote liver regeneration.
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影响因子：
9.7
作者：
Ma Y;Temkin SM;Hawkridge AM;Guo C;Wang W;Wang XY;Fang X
通讯作者：
Fang X
影响因子：
5
作者：
Arab, Hany H.;Safar, Marwa M.;Shahin, Nancy N.
通讯作者：
Shahin, Nancy N.
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
4.8
作者：
Bellet, Marina Maria;Masri, Selma;Servillo, Giuseppe
通讯作者：
Servillo, Giuseppe
影响因子：
3.3
作者：
Davidson, Ben;Hadar, Rivka;Reich, Reuven
通讯作者：
Reich, Reuven