Zou Dongbin, Yang Yun, Ji Fengjie, Lv Renlong, Xu Tieshan, Hu Chengjun
Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China.
College of Life Sciences, Hainan University, Haikou 571101, China.
Antioxidants (Basel). 2023 Sep 25;12(10):1800. doi: 10.3390/antiox12101800.
Intestinal vessels play a critical role in nutrient absorption, whereas the effect and mechanism of low birth weight (LBW) on its formation remain unclear. Here, twenty newborn piglets were assigned to the control (CON) group (1162 ± 98 g) and LBW group (724 ± 31 g) according to their birth weight. Results showed that the villus height and the activity of maltase in the jejunum were lower in the LBW group than in the CON group. LBW group exhibited a higher oxidative stress level and impaired mitochondrial function in the jejunum and was lower than the CON group in the intestinal vascular density. To investigate the role of oxidative stress in intestinal angiogenesis, HO was employed to induce oxidative stress in porcine intestinal epithelial cells (IPEC-J2). The results showed that the conditioned media from IPEC-J2 with HO treatment decreased the angiogenesis of porcine vascular endothelial cells (PVEC). Transcriptome analysis revealed that a higher expression level of dual oxidase 2 (DUOX2) was found in the intestine of LBW piglets. Knockdown of DUOX2 in IPEC-J2 increased the proliferation and decreased the oxidative stress level. In addition, conditioned media from IPEC-J2 with DUOX2-knockdown was demonstrated to promote the angiogenesis of PVEC. Mechanistically, the knockdown of DUOX2 decreased the reactive oxygen species (ROS) level, thus increasing the angiogenesis in a matrix metalloproteinase 3 (MMP3) dependent manner. Conclusively, our results indicated that DUOX2-induced oxidative stress inhibited intestinal angiogenesis through MMP3 in a LBW piglet model.
肠道血管在营养物质吸收中起着关键作用，而低出生体重（LBW）对其形成的影响及机制尚不清楚。在此，根据出生体重将20只新生仔猪分为对照组（CON组，1162±98 g）和低出生体重组（LBW组，724±31 g）。结果显示，LBW组空肠绒毛高度和麦芽糖酶活性低于CON组。LBW组空肠氧化应激水平较高，线粒体功能受损，肠道血管密度低于CON组。为研究氧化应激在肠道血管生成中的作用，采用过氧化氢（HO）诱导猪肠道上皮细胞（IPEC-J2）产生氧化应激。结果显示，HO处理的IPEC-J2条件培养基降低了猪血管内皮细胞（PVEC）的血管生成。转录组分析显示，LBW仔猪肠道中双氧化酶2（DUOX2）表达水平较高。在IPEC-J2中敲低DUOX2可增加细胞增殖并降低氧化应激水平。此外，敲低DUOX2的IPEC-J2条件培养基可促进PVEC的血管生成。机制上，敲低DUOX2可降低活性氧（ROS）水平，从而以基质金属蛋白酶3（MMP3）依赖的方式增加血管生成。总之，我们的结果表明，在低出生体重仔猪模型中，DUOX2诱导的氧化应激通过MMP3抑制肠道血管生成。
