通过血红素介导的肝素诱导需要骨形态遗传蛋白 I 型受体 ALK2 和 ALK3
Deniz Y Dogan1,2, Eugen I Urzica3, Isabelle Hornung1
1Department of Anesthesiology, Goethe University Frankfurt, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.
Blood advances
|April 8, 2024
概括
血红素 (HJV) 需要BMP受体ALK2和ALK3来诱导肝素和调节铁. 这些受体的肝脏特异性缺陷阻止HJV在小鼠中纠正铁过载.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 血红素 (HJV) 是铁平衡的关键调节剂,作为骨形态蛋白 (BMP) 核心受体,刺激肝素的产生.
- 肝素通过降解铁酸铁出口剂来控制铁的吸收和释放.
- 在体内信号通路的HJV仍然不完全理解.
研究的目的:
- 调查BMP I型受体ALK2和ALK3在HJV介导的肝素诱导中的体内作用.
- 为了确定HJV是否可以在肝细胞特异性ALK2或ALK3.3缺乏的小鼠中拯救铁过载表型.
主要方法:
- 在小鼠模型中,腺相关病毒 (AAV) 介导的肝脏特异性HJV过度表达.
- 使用BMP I型受体Alk2和Alk3 (Alk2fl/fl;Alb-Cre和Alk3fl/fl;Alb-Cre小鼠) 的肝细胞特异性缺陷模型.
- 评估了肝脏的Hamp mRNA,可溶性HJV (sHJV),脏铁含量 (SIC),血清铁,以及化SMAD蛋白 (pSMAD1/5/8).
主要成果:
- 在对照小鼠中,HJV过度表达增加了Hamp mRNA,sHJV,SIC和pSMAD水平.
- 在Alk2和Alk3缺乏的小鼠中,AAV-HJV的管理增加了HJV和sHJV,但没有解决过量的铁.
- 在缺乏肝细胞ALK2或ALK3的小鼠中,尽管血清铁和铁蛋白水平高,但HJV的肝素诱导受损.
结论:
- 在体内,ALK2和ALK3都对HJV有效诱导肝激素至关重要.
- 肝细胞中介的铁调节严重依赖于肝细胞中ALK2和ALK3的存在和功能.
- 这些发现突出了ALK2/ALK3-HJV轴作为系统铁平衡的关键组成部分.
相关概念视频
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
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
Hematopoiesis
5.2K
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
5.2K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
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
Overview of Hematopoiesis
4.0K
Hematopoiesis, or blood cell production, is a vital biological process that begins early in embryonic development and continues throughout life. This process generates the various types of cells found in blood, including red blood cells, white blood cells, and platelets from hematopoietic stem cells (HSCs).
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
4.0K


