Phenobarbital, a hepatic metabolic enzyme inducer, inhibits preneoplastic hepatic lesions with expression of selective autophagy receptor p62 and ER-phagy receptor FAM134B in high-fat diet-fed rats through the inhibition of ER stress.
Phenobarbital, a hepatic metabolic enzyme inducer, inhibits preneoplastic hepatic lesions with expression of selective autophagy receptor p62 and ER-phagy receptor FAM134B in high-fat diet-fed rats through the inhibition of ER stress.
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DOI：
10.1016/j.fct.2023.113607
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发表时间：
2023-01
期刊：
影响因子：
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通讯作者：
Suzuka Uomoto;Keisuke Takesue;Saori Shimuzu;Natsuno Maeda;Kana Ohshima;E. Hara;Mio Kobayashi
中科院分区：
文献类型：
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作者：
Suzuka Uomoto;Keisuke Takesue;Saori Shimuzu;Natsuno Maeda;Kana Ohshima;E. Hara;Mio Kobayashi
我们通过对肿瘤前肝病变中选择性自噬受体p62和ER吞噬特异性受体FAM134B的表达水平进行聚类，研究了高脂饮食（HFD）喂养和/或苯巴比妥（PB）治疗的大鼠内质网（ER）吞噬在nafld相关肝癌发生中的作用。我们获得了肿瘤前病变中p62和FAM134B表达水平可变的4个簇，每组中簇的数量都是可变的。PB使p62高表达的细胞群增加，HFD使p62和FAM134B高表达的细胞群增加。p62和FAM134B低表达组肿瘤前病变面积明显增加。HFD与PB联合饲喂可抵消二者的影响，种群组成与对照组相似。结果与内质网应激、炎症细胞因子、自噬基因表达降低和抗氧化酶表达增加有关。本研究表明，聚类分析有助于了解自噬在各肿瘤前病变中的作用，HFD喂养通过抑制er吞噬而增加肿瘤前病变，而PB通过诱导er吞噬而抵消了这一作用。
We investigated the role of endoplasmic reticulum (ER)-phagy in NAFLD-related hepatocarcinogenesis in high-fat diet (HFD)-fed and/or phenobarbital (PB)-treated rats by clustering the expression levels of the selective autophagy receptor p62 and the ER-phagy-specific receptor FAM134B in preneoplastic hepatic lesions. We obtained four clusters with variable expression levels of p62 and FAM134B in preneoplastic lesions, and a variable population of clusters in each group. PB administration increased the clusters with high expression levels of p62 while HFD feeding increased the clusters with high expression levels of both p62 and FAM134B. The areas of preneoplastic lesions of these clusters were significantly increased than those of other clusters with low expression levels of p62 and FAM134B. The combination of HFD feeding with PB counteracted the effects of each other, and the cluster composition was similar to that in the control group. The results were associated with decreased gene expression of ER stress, inflammatory cytokine, autophagy, and increased expression of antioxidant enzyme. The present study demonstrated that clustering analysis is useful for understanding the role of autophagy in each preneoplastic lesion, and that HFD feeding increased preneoplastic lesions through the inhibition of ER-phagy, which was cancelled with PB administration through the induction of ER-phagy.