JNK媒介のTNF-α発現によって肝炎を誘発する
Madhumita Das1, Guadalupe Sabio, Feng Jiang
1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell
|January 27, 2009
まとめ
c-Jun NH2端末キナーゼ (JNK) 経路は,肝炎発症中に,肝細胞死亡ではなく,腫瘍死滅因子 (TNF) -alphaの発現に極めて重要です.
科学分野:
- 免疫学 免疫学とは
- 肝臓病理学 肝臓病理学
- 分子生物学は分子生物学である.
背景:
- c-Jun NH2端末キナーゼ (JNK) 信号伝達経路は,腫瘍死滅因子 (TNF) 依存性肝炎に関与しています.
- TNF刺激による肝細胞死におけるJNKの役割は,体内でのさらなる調査が必要である.
研究 の 目的:
- TNF依存性肝炎の発症におけるJNK1とJNK2の役割を調査する.
- 肝炎の進行のために肝細胞または血液生成細胞においてJNKが不可欠であるかどうかを判断する.
主な方法:
- Jnk1およびJnk2遺伝子の複合障害を持つマウスの世代.
- 肝細胞特異的または血液形成特異的JNK1/2欠乏症のマウスにおける肝炎現象型の分析.
- TNF-α発現と肝損傷の評価.
主要な成果:
- 肝細胞にJNK1/2が欠けているマウスは,肝炎発達の欠陥を示さなかった.
- 血液形成細胞にJNK1/2が欠けていたマウスは,肝炎の有意な欠陥を示した.
- JNK欠乏したマウスの肝炎は,TNF-α発現の低下と関連していました.
- TNF-αは,肝細胞特異的なJNK1/2-欠乏症のマウスと対照マウスの両方に同様の肝損傷を引き起こした.
結論:
- JNKはTNF-α発現に不可欠ですが,TNF-α誘発の肝細胞死亡には欠かせません.
- 肝細胞ではなく,血液形成細胞は,肝炎の発症におけるJNK機能の重要な部位である.
関連する概念動画
Hepatitis
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
Cirrhosis II: Pathophysiology
Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to structural...
Viral Hepatitis I: Introduction
Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...
Liver Regeneration
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 large...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...


