Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia.
Neurogastroenterol Motil. 2011 May;23(5):475-83, e179-80. doi: 10.1111/j.1365-2982.2011.01685.x. Epub 2011 Feb 22.
In the intestine, the tachykinins substance P (SP) and neurokinin A (NKA) are found in neurons and have key roles in motility, secretion, and immune functions. A new tachykinin, hemokinin (HK-1), has been identified in non-neuronal cells in recent years and its role in intestinal inflammation is unclear. We aimed to examine the expression of genes encoding tachykinin peptides and receptors in colon from patients with ulcerative colitis (UC), Crohn's disease (CD), and acute diverticular disease (DD).
Human colon segments were dissected into mucosa and muscle, and evaluated for tachykinin and tachykinin receptor gene expression by real-time PCR.
In UC mucosa, the TAC4 gene (encoding HK-1) was 10-fold more abundant than in control mucosa (P < 0.01). Similarly, TAC1 (encoding SP and NKA) and TACR1 (encoding NK1 receptor) displayed 6-fold and 12-fold upregulation, respectively, in UC mucosa, but no change occurred in UC muscle. In contrast to UC, no difference was observed for any tachykinin genes in CD mucosa. In CD muscle, expression of TAC1 (P < 0.01), TAC4 and TACR1 (both P < 0.05) were moderately upregulated. In DD, there was a decrease in TACR1 (P < 0.05), and TACR2 (encoding NK2 receptor, P < 0.0001) in muscle compared with control. Histological staining showed increased collagen fibers between muscle bundles in DD smooth muscle.
CONCLUSIONS & INFERENCES: We provide evidence for the first time that HK-1, like SP, may be involved in the pathophysiology of inflammatory bowel disease. Distinctly different expression patterns of tachykinin-related genes occur in UC, CD and DD.
在肠道中，速激肽物质 P（SP）和神经激肽 A（NKA）存在于神经元中，在运动、分泌和免疫功能中发挥关键作用。近年来，在非神经元细胞中发现了一种新的速激肽，即血激肽（HK-1），但其在肠道炎症中的作用尚不清楚。我们旨在研究溃疡性结肠炎（UC）、克罗恩病（CD）和急性憩室炎（DD）患者结肠中编码速激肽肽和受体的基因表达。
将人结肠段解剖为黏膜和肌肉，并通过实时 PCR 评估速激肽和速激肽受体基因的表达。
在 UC 黏膜中，TAC4 基因（编码 HK-1）的丰度比对照黏膜高 10 倍（P < 0.01）。同样，TAC1（编码 SP 和 NKA）和 TACR1（编码 NK1 受体）在 UC 黏膜中的表达分别上调了 6 倍和 12 倍，但在 UC 肌肉中没有变化。与 UC 相反，CD 黏膜中没有观察到任何速激肽基因的差异。在 CD 肌肉中，TAC1（P < 0.01）、TAC4 和 TACR1（均 P < 0.05）的表达中度上调。在 DD 中，与对照相比，肌肉中的 TACR1（P < 0.05）和 TACR2（编码 NK2 受体，P < 0.0001）表达减少。组织学染色显示 DD 平滑肌中肌肉束之间的胶原纤维增加。
我们首次提供证据表明，HK-1 可能像 SP 一样参与炎症性肠病的病理生理学。在 UC、CD 和 DD 中，速激肽相关基因的表达模式明显不同。
