Mechanisms of Chemically Induced Glomerular Injury
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
The location and properties of the glomerular mesangial cells confer a central role for these cells in the regulation of renal function. Mesangium is composed of mesangial cells and MM.17 Mesangial cells are located within the central portion of the glomerular tuft between capillary loops3,18 and connect through gap junctions with each other as well as with the lacis cells of the extraglomerular mesangium, and with the juxtaglomerular granular cells. The glomerular MM and mesangial cells are separated from the capillary lumen by a fenestrated endothelium (Figure 4). Thus mesangial cells are constantly percolated by plasma from glomerular capillaries and are continuously exposed to various types of cells, macromolecules, immune complexes, and circulating or locally released hormones and mediators.19
Functions of the Kidneys and Functional Anatomy
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The renal corpuscles, in the cortex of the kidney, comprise tufts of glomerular capillaries in distinct loops that invaginate Bowman's capsules. Fluid is filtered from the glomerular capillaries into Bowman's space under the action of opposing hydrostatic and oncotic pressures. The glomerular capillaries are supplied by an afferent arteriole and are drained by a second, efferent, arteriole. The filtration barrier to the movement of fluid and solutes from the glomerular capillary to Bowman's space comprises the capillary endothelium, a layer of basement membrane, and the capsular epithelial cells, the podocytes. The capillary endothelium has many perforations, or fenestrae. The podocytes have many lengthened foot processes, which overlap and are embedded in the basement membrane layer. There are slits between the foot processes, and these are covered by very thin diaphragms. Mesangial cells are found in close association with the capillary loops of the glomerulus. The glomerular mesangial cells have a phagocytic function and remove trapped material from the basement membrane. Myofilaments in the mesangial cells enable the cells to contract or relax in response to stimuli, similar to vascular smooth muscle, thereby altering the surface area available for diffusion across the glomerular capillary membrane.
Nutrition, Chronic Kidney Disease, and Kidney Failure
David Heber, Zhaoping Li in Primary Care Nutrition, 2017
The most common cause of chronic renal insufficiency is diabetes (Vallon and Thomson 2012). After 10–20 years of diabetes mellitus, approximately 20% of patients with either type 1 or type 2 diabetes mellitus develop diabetic nephropathy, making diabetes mellitus the leading cause of ESRD. Both genetic and environmental factors determine which patients eventually develop diabetic nephropathy, and there remains a need for research to better understand the pathophysiology and molecular pathways that lead from the onset of hyperglycemia to renal failure. Changes in the vasculature and the glomerulus, including those to mesangial cells, the filtration barrier, and podocytes, play important roles in the pathophysiology of the diabetic kidney.
High glucose and TGF-β1 reduce expression of endoplasmic reticulum-resident selenoprotein S and selenoprotein N in human mesangial cells
Published in Renal Failure, 2019
Fumeng Huang, Yuanxu Guo, Li Wang, Lanmei Jing, Zhao Chen, Shemin Lu, Rongguo Fu, Lifang Tian
Renal fibrosis is the common pathway and final outcome of various progressive chronic kidney disease including diabetic nephropathy. The key pathological change of diabetic nephropathy is proliferation and hypertrophy of mesangial cells, excessive accumulation of extracellular matrix (ECM) proteins which eventually leads to nodular glomerulosclerosis [1,2]. Mesangial cells are the intrinsic cells of the glomerulus. They can produce ECM, secrete fibronectin, phagocytose, remove foreign bodies and regulate capillary blood flow in the glomerulus [3]. In pathological conditions, high expression of fibronectin leads to renal fibrosis. Oxidative stress and endoplasmic reticulum (ER) stress are important factors to the ECM glomerular pathology in diabetic nephropathy [4,5] and in unilateral ureteral renal fibrosis mouse model or kidney cells stimulated by transforming growth factor-β1 (TGF-β1) [5,6]. Hyperglycemia in diabetic nephropathy generates elevated levels of reactive oxygen species (ROS) which induce kidney damage. Both high glucose (HG) and TGF-β1 could induce the production of ROS in mesangial cells [6,7].
Role of advanced glycation end products and insulin resistance in diabetic nephropathy
Published in Archives of Physiology and Biochemistry, 2023
Many growing bodies of evidence suggest the role of AGEs induced ER stress in the development and progression of DN. More specifically, AGEs and advanced oxidation protein products (AOPPs) have been shown to induce ER stress in cultured podocytes leading to apoptosis in murine podocytes (Chen et al. 2008, Rong et al. 2015). Upregulation of ER stress markers was observed in podocytes treated with high glucose concentrations resulting in their cell death (Cao et al. 2014). Mesangial cells are essential to maintain the integrity of glomerulus and also play an important role in maintaining glomerular filtration (Fan et al. 2017). Mesangial cells are the most susceptible to the damage induced due to high glucose along with increased ROS. Exposure to high glucose leads to proliferation of mesangial cells resulting in overproduction of extracellular matrix (ECM), which was suppressed by overexpression of XBP-1s (Shao et al. 2013).
Oxidative stress and histopathological changes in several organs of mice injected with biogenic silver nanoparticles
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Shushanik Kazaryan, Lilit Farsiyan, Juleta Tumoyan, Gayane Kirakosyan, Naira Ayvazyan, Hrachik Gasparyan, Sona Buloyan, Lilit Arshakyan, Ara Kirakosyan, Ashkhen Hovhannisyan
Although the exposure to O. araratum did not affect the overall structure of the liver, the extract caused heavy portal hypertension. In this group, acute congestion of central veins, sinusoidal dilation and hemostasis was observed. These haemodynamic changes lead to liver ischaemia, which in turn caused focal necrosis and pyknosis of the hepatocytes. Along with this, the onset of microvesicular steatosis was observed (Figure 8). Statistical analysis of all parameters in liver tissue showed significant differences between the control group and mice treated with O. araratum (p < .05). Examination of renal tissue showed that exposure to O. araratum extract leads to acute tubular necrosis, which is accompanied by glomerulonephritis. In the glomeruli of the renal tissue, foci of diffuse proliferation of mesangial cells have been revealed. In the lumen of the tubules, sloughed-off necrotic epithelial cells and granular casts were observed (Figure 8). The statistical analysis of these parameters also revealed significant differences compared to control animals (p < .05).
Related Knowledge Centers
- Actin
- Afferent Arterioles
- Efferent Arteriole
- Glomerulus
- Myosin
- Renal Corpuscle
- Capillary
- Kidney
- Extraglomerular Mesangial Cell
- Intraglomerular Mesangial Cell