PTGER4信号调节直肠上皮细胞中的IIa类HDAC功能和SPINK4mRNA水平
Murugadas Anbazhagan1, Garima Sharma1, Shanta Murthy1
1Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Emory University School of Medicine, Emory University, Atlanta, GA, USA.
Cell communication and signaling : CCS
|October 13, 2024
概括
介酶体 stromal 细胞 (MSC) 使用前列腺素 E2 (PGE2) 激活肠道上皮细胞中的 PTGER4 信号,增加 SPINK4 mRNA 和蛋白质释放,特别是在粘膜损伤期间.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 前列腺素受体PTGER4在肠道平衡中起作用.
- 杯状细胞SPINK4表达可能受到PTGER4.4的影响.
- 介酶体 stromal 细胞 (MSC) 在炎症期间在上皮细胞中产生前列腺素E2 (PGE2),刺激PTGER4.
研究的目的:
- 研究皮质细胞中PTGER4活性的亚细胞机制.
- 确定受PTGER4信号影响的下游mRNA水平.
- 阐明MSC衍生PGE2在调节SPINK4表达中的作用.
主要方法:
- 在共同培养系统中利用患者衍生的粘膜细胞,器官和MSC.
- 使用PGE2,化学抑制剂 (L-161982,LMK-235),酸盐来操纵PTGER4活性和下游目标.
- 采用免疫光学,单细胞测序,RNAscope,ELISA,实时PCR和西式斑点进行分析.
主要成果:
- 在MSC共同培养或PGE2刺激中,SPINK4mRNA水平增加,由PTGER4 (L-161982) 或HDAC4 (LMK-235) 抑制剂抑制.
- PTGER4定位在直肠上皮细胞的底侧表面.
- PGE2降低了HDAC4,5和7的酸化,这种效应被L-161982逆转;丁酸盐或L-161982增加了酸化.
结论:
- 在粘膜损伤期间,MSC衍生的PGE2可提高皮质细胞中PTGER4信号的调节.
- 这种信号通路增加了HDAC4,5和7的活性.
- 最终导致SPINK4mRNA水平升高和细胞外释放.
相关概念视频
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
Activation and Inactivation of G Proteins
6.8K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.8K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
The Ras Gene
6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.2K


