胰岛素受体信号引发膀泌尿道防御,限制尿路感染
Laura Schwartz1, Kristin Salamon2, Aaron Simoni2
1The Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's, Columbus, OH 43205, USA; Division of Nephrology and Hypertension, Nationwide Children's, Columbus, OH 43205, USA.
Cell reports
|March 22, 2024
概括
糖尿病患者容易患上尿路感染 (UTI). 这项研究表明,激活膀中的胰岛素受体 (IR) 通过维持屏障功能和抗菌来预防尿路感染.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 糖尿病是尿路感染 (UTI) 的重要危险因素.
- 糖尿病与增加的尿路感染易感性相关的潜在机制尚未完全理解.
- 胰岛素信号通路与各种细胞功能有关,包括免疫反应和组织完整性.
研究的目的:
- 研究胰岛素受体 (IR) 在尿膜在糖尿病中抵抗尿路感染的作用.
- 阐明红外信号影响膀屏障功能和抗菌防御的分子机制.
主要方法:
- 利用糖尿病小鼠模型与改变的胰岛素信号.
- 检查了膀泌尿道细胞中的IR表达和功能.
- 评估了对尿病原性大肠杆菌 (UPEC) 感染的敏感性.
- 分析了泌尿道屏障完整性和抗微生物的表达.
- 来自糖尿病患者的人类生物样本的验证结果.
主要成果:
- 糖尿病小鼠表现出抑制的红外表达和对UPEC的敏感性增加.
- 系统性IR抑制加剧了尿路感染的易感性,而IR激活则提供了保护.
- 在膀泌尿中局部IR删除增加了通过损害屏障透性和减少抗菌来增加尿路感染的易感性.
- 红外线删除减少了核因子kB (NF-kB) 依赖于泌尿器密集结和抗菌的调节.
- 来自糖尿病年轻人的人类生物样本显示IR,屏障基因和抗微生物的表达减少.
结论:
- 由胰岛素受体介导的尿路胰岛素信号传递在预防尿路感染方面发挥着至关重要的作用.
- 红外线对于维持泌尿道屏障完整性和表达抗菌是必不可少的.
- 糖尿病中功能障碍的红外线信号有助于通过障碍功能和减少宿主防御来增加尿路感染的易感性.
相关概念视频
01:28Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
01:26The Micturition Reflex
587
Urination, or micturition involves the coordination of the bladder's detrusor muscle and two sphincters to ensure controlled bladder emptying.
The process begins with bladder filling, where the bladder wall stretches as urine accumulates. This stretching activates the urine storage reflex, mediated by the sacral spinal segments and the pontine storage center. Efferent sympathetic impulses stimulate the detrusor muscle to relax and the internal urethral sphincter to contract, facilitating...
The process begins with bladder filling, where the bladder wall stretches as urine accumulates. This stretching activates the urine storage reflex, mediated by the sacral spinal segments and the pontine storage center. Efferent sympathetic impulses stimulate the detrusor muscle to relax and the internal urethral sphincter to contract, facilitating...
587
01:45Endocrine Signaling
64.3K
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
64.3K
01:26Defense Mechanism Against Infection
6.5K
Natural flora, body system defenses, and inflammation are natural barriers of the body against infectious agents regardless of previous exposure. Normal floras of the human body refer to the microbial population that colonizes the skin and mucous membranes.
In addition, many body organ systems have unique defenses against infection. The skin is an intact, multilayered surface preventing invasion by microorganisms unless impaired. Mucous membranes lining the mouth, nose, and eyelids are barriers...
In addition, many body organ systems have unique defenses against infection. The skin is an intact, multilayered surface preventing invasion by microorganisms unless impaired. Mucous membranes lining the mouth, nose, and eyelids are barriers...
6.5K
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K