增长分化因子7自身隐性信号传递促进肝纤维化时的肝原生细胞扩张
Defu Kong1, Apostolos Mourtzinos1, Janette Heegsma1
1Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Stem cell research & therapy
|October 5, 2023
概括
增长分化因子7 (GDF7) 在肝纤维化时升高,可能促进肝脏再生. 这一发现表明GDF7可能是治疗慢性肝病的治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 再生医学是一种再生医学.
背景情况:
- 肝纤维化是慢性肝病的普遍后果,对全球健康构成重大挑战.
- 在慢性肝病中,TGFβ超级家族成员生长差异化因子7 (GDF7) 的作用仍然在很大程度上未被探索.
- 了解GDF7在肝脏中的功能对于开发新的治疗策略至关重要.
研究的目的:
- 为了研究GDF7在人肝纤维化中的表达.
- 为了确定人类肝脏内GDF7的细胞来源和点.
- 探索GDF7在肝脏再生和纤维化中的潜在作用.
主要方法:
- 免疫组织化学和qPCR分析健康和纤维化的人类肝脏组织中的GDF7表达.
- 免疫光和共同染色用于GDF7.7的细胞特异定位.
- 对GDF7表达模式的公共单细胞RNA测序数据的分析.
- 在体外研究中,使用人肝器官和用重组GDF7.7治疗的LX-2肝硬细胞进行了实验.
主要成果:
- 在纤维化肝脏组织中,GDF7蛋白和mRNA水平升高,主要在肝细胞和胆细胞中.
- 在肝细胞,胆管细胞和星状细胞中检测到GDF7受体 (BMPR1A,BMPR2).
- 复合GDF7在体外促进了肝脏有机体的生长和原始细胞标记物表达 (LGR5,AXIN2).
- 激活的肝星细胞诱导了GDF7和LGR5在共同培养的肝脏有机体中的表达.
结论:
- 在人类肝纤维化中,GDF7的表达增加.
- GDF7在肝脏有机体中表现出潜在的亲再生性质.
- GDF7可能在肝星细胞与肝脏再生之间的相互作用中发挥作用.
- GDF7代表了改善肝纤维化的潜在治疗标.
相关概念视频
Liver Regeneration
3.3K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K
Role of Hematopoietic Growth Factors
1.4K
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
1.4K
Tissue Renewal without Stem Cells
1.7K
After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
However, failure of such a system...
However, failure of such a system...
1.7K
Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
TGF - β Signaling Pathway
7.4K
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...
7.4K
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K


