刺猬信号通路及其在肠道上皮结构形成中的作用。

Hedgehog Signalling Pathway and Its Role in Shaping the Architecture of Intestinal Epithelium.

机构信息

Laboratory of Analysis of Gastrointestinal Tract Protective Barrier, Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.

Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.

出版信息

Int J Mol Sci. 2024 Nov 8;25(22):12007. doi: 10.3390/ijms252212007.

Abstract

The hedgehog (Hh) signalling pathway plays a key role in both embryonic and postnatal development of the intestine and is responsible for gut homeostasis. It regulates stem cell renewal, formation of the villous-crypt axis, differentiation of goblet and Paneth cells, the cell cycle, apoptosis, development of gut innervation, and lipid metabolism. Ligands of the Hh pathway, i.e., Indian hedgehog (Ihh) and Sonic hedgehog (Shh), are expressed by superficial enterocytes but act in the mesenchyme, where they are bound by a Patched receptor localised on myofibroblasts and smooth muscle cells. This activates a cascade leading to the transcription of target genes, including those encoding G1/S-specific cyclin-D2 and -E1, B-cell lymphoma 2, fibroblast growth factor 4, and bone morphogenetic protein 4. The Hh pathway is tightly connected to Wnt signalling. Ihh is the major ligand in the Hh pathway. Its activation inhibits proliferation, while its blocking induces hyperproliferation and triggers a wound-healing response. Thus, Ihh is a negative feedback regulator of cell proliferation. There are data indicating that diet composition may affect the expression of the Hh pathway genes and proteins, which in turn, induces changes in mucosal architecture. This was shown for fat, vitamin A, haem, berberine, and ovotransferrin. The Hh signalling is also affected by the intestinal microbiota, which affects the intestinal barrier integrity. This review highlights the critical importance of the Hh pathway in shaping the intestinal mucosa and summarises the results obtained so far in research on the effect of dietary constituents on the activity of this pathway.

摘要

刺猬(Hh)信号通路在肠道的胚胎和出生后发育中起着关键作用,负责肠道内稳态。它调节干细胞更新、绒毛-隐窝轴的形成、杯状细胞和潘氏细胞的分化、细胞周期、细胞凋亡、肠道神经支配的发育和脂质代谢。Hh 途径的配体,即印度刺猬(Ihh)和 Sonic 刺猬(Shh),由表面肠细胞表达,但在间质中起作用,在间质中,它们被定位在肌成纤维细胞和平滑肌细胞上的 Patched 受体结合。这激活了一个级联反应,导致靶基因的转录,包括编码 G1/S 特异性周期蛋白-D2 和 -E1、B 细胞淋巴瘤 2、成纤维细胞生长因子 4 和骨形态发生蛋白 4 的基因。Hh 途径与 Wnt 信号紧密相连。Ihh 是 Hh 途径中的主要配体。其激活抑制增殖,而其阻断则诱导过度增殖并引发伤口愈合反应。因此,Ihh 是细胞增殖的负反馈调节剂。有数据表明,饮食成分可能影响 Hh 途径基因和蛋白质的表达,进而引起粘膜结构的变化。这在脂肪、维生素 A、血红素、小檗碱和卵转铁蛋白中得到了证明。Hh 信号也受到肠道微生物群的影响,肠道微生物群影响肠道屏障的完整性。这篇综述强调了 Hh 途径在塑造肠道粘膜中的重要性,并总结了迄今为止关于饮食成分对该途径活性影响的研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb4/11593361/ac0719110ec2/ijms-25-12007-g001.jpg

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