Li Wangchang, Chen Wenxin, Wang Yancan, Wang Qianqian, Yang Huansheng, Wang Qiye, Wang Bin
Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
Yuelushan Laboratory, Changsha 410128, China.
Animals (Basel). 2025 Aug 18;15(16):2419. doi: 10.3390/ani15162419.
The ileum serves as the primary site for nutrient digestion and absorption in the intestine, with villus height representing a critical indicator of intestinal absorptive capacity. To investigate the regulatory mechanisms underlying ileal villus development, we conducted a feeding trial using crossbred pigs (Duroc × Landrace × Yorkshire) with an initial body weight of 27.74 ± 0.28 kg, stratifying them into high-villus and low-villus groups based on ileal villus height (n = 4). The results revealed 849 differentially RNA-edited genes (REGs) between the two groups, including 472 hyper-edited genes in the low-villus group and 377 in the high-villus group. Functional enrichment analysis showed that these REGs were significantly enriched in inflammation-related pathways, particularly the TNF signaling pathway and IL-17 signaling pathway, with TNF pathway genes exhibiting notably higher editing levels in the high-villus group. Additionally, 46 differentially expressed genes (DEGs) were identified, comprising 22 upregulated in the low-villus group and 24 in the high-villus group, which were similarly enriched in TNF and IL-17 signaling pathways. Integrated quadrant analysis of the RNA editing and transcriptomic profiles demonstrated that pro-inflammatory genes CXCL10 (C-X-C motif chemokine 10), CCL2 (C-C motif chemokine ligand 2), CREB3L2 (CAMP-responsive element-binding protein 3-like 2), and PIK3R1 (Phosphoinositide-3-kinase regulatory subunit 1) were highly expressed in the low-villus group but exhibited significantly lower RNA editing levels compared to the high-villus group. Furthermore, the expression of the inflammation-suppressive RNA editing enzyme APOBEC1 (apolipoprotein B mRNA editing enzyme catalytic subunit 1) showed correlation with villus height (R = 0.81, < 0.05). Collectively, our findings indicate that RNA editing dynamics influence the variation in ileal villus height within inflammation-associated pathways, particularly the TNF signaling pathway. Enhanced RNA editing of this pathway may mitigate intestinal inflammation and promote healthy ileal villus developments.
回肠是肠道中营养物质消化和吸收的主要部位，绒毛高度是肠道吸收能力的关键指标。为了研究回肠绒毛发育的调控机制，我们使用初始体重为27.74±0.28 kg的杂交猪（杜洛克×长白×约克夏）进行了一项饲养试验，根据回肠绒毛高度将它们分为高绒毛组和低绒毛组（n = 4）。结果显示，两组之间有849个差异RNA编辑基因（REGs），其中低绒毛组有472个高编辑基因，高绒毛组有377个。功能富集分析表明，这些REGs在炎症相关通路中显著富集，特别是TNF信号通路和IL-17信号通路，高绒毛组中TNF通路基因的编辑水平明显更高。此外，还鉴定出46个差异表达基因（DEGs），其中低绒毛组上调22个，高绒毛组上调24个，它们同样在TNF和IL-17信号通路中富集。RNA编辑和转录组图谱的综合象限分析表明，促炎基因CXCL10（C-X-C基序趋化因子10）、CCL2（C-C基序趋化因子配体2）、CREB3L2（CAMP反应元件结合蛋白3样2）和PIK3R1（磷脂酰肌醇-3-激酶调节亚基1）在低绒毛组中高表达，但与高绒毛组相比，其RNA编辑水平显著降低。此外，炎症抑制性RNA编辑酶APOBEC1（载脂蛋白B mRNA编辑酶催化亚基1）的表达与绒毛高度相关（R = 0.81，P < 0.05）。总的来说，我们的研究结果表明，RNA编辑动态影响炎症相关通路中回肠绒毛高度的变化，特别是TNF信号通路。该通路中增强的RNA编辑可能减轻肠道炎症并促进回肠绒毛的健康发育。
