铁通过PTEN/PI3 K/AKT/FOXO1通路调节血友性软骨中的冠状细胞表型
Liujie Zheng1,2, Yunfeng Yao2, Dasheng Luo2
1Department of Orthopaedic Surgery, The Fourth Hospital of Wuhan, Wuhan, People's Republic of China.
Hematology (Amsterdam, Netherlands)
|July 26, 2023
概括
铁过载通过改变状细胞表型,导致血友性软骨的破坏. 这项研究表明,铁抑制PTEN/PI3K/AKT/FOXO1通路,影响软骨健康.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 整形外科 整形外科 整形外科
背景情况:
- 铁过载与血友性软骨破坏有关.
- 之前的研究表明,铁会影响状细胞表型,细胞亡和细胞外基质降解.
- 铁对血友性关节炎中软骨细胞的影响的确切机制尚不清楚.
研究的目的:
- 阐明铁在血友性软骨破坏中影响状细胞表型的机制.
- 调查PTEN/PI3K/AKT/FOXO1信号通路在铁诱导的冠状细胞变化中的作用.
主要方法:
- 西方斑点分析用于评估血友性关节炎 (HA) 和骨关节炎 (OA) 患者的关节软骨中的蛋白质表达.
- 初级人类正常红细胞被用不同度的铁治疗,以量化PTEN/PI3K/AKT/FOXO1通路组件的变化.
- 测量了包括PTEN,PI3K,p-PI3K,AKT,p-AKT,FOXO1和p-FOXO1在内的关键蛋白质.
主要成果:
- 与OA患者相比,患有HA的患者在关节软骨中表现出上调的PTEN,PI3K,AKT和FOXO1,以及下调的p-PI3K,p-AKT和p-FOXO1.
- 红细胞中铁的暴露导致了PTEN,PI3K,AKT和FOXO1表达的剂量依赖性增加.
- 铁还抑制了细胞中PI3K,AKT和FOXO1 (p-PI3K,p-AKT,p-FOXO1) 的酸化,这取决于剂量.
结论:
- 铁过载在血友性软骨破坏的发病过程中起作用.
- 铁通过抑制PTEN/PI3K/AKT/FOXO1信号通路来影响状细胞的表型.
- 这种途径的抑制是导致血友性关节炎中软骨损伤的关键机制.
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
Growth of Cartilage and Bone Tissue
3.4K
Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
3.4K
Bone Formation by Endochondral Ossification
4.7K
Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
4.7K
PI3K/mTOR/AKT Signaling Pathway
3.7K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.7K
Hedgehog Signaling Pathway
7.4K
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...
7.4K


