Mesangial Cells

Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

Mesangial cells are the smooth muscle-like cells of the capillaries in the glomerulus of the kidney. 

PDE1C2 and PDE4A are expressed. PDE1C2 is found in the cilia of the epithelium, where it colocalizes with adenylyl cyclase. PDE4A is found throughout the epithelial layer, but not in cilia. Therefore, as in the kidney mesangial cells, different PDEs must be working on different cyclic nucleotide pools. More recently, substantial data has been developed for compartmenta-tion of cAMP and PDEs in cardiac myocytes. 

In the interstitium, angiotensin II induces proliferation of mesangial cells and fibroblasts and the synthesis of collagen and other matrix molecules by these cells via the ATI receptor. Moreover, by the concomitant stimulation of chemoattractant cytokines, inflammation is induced. These processes are mediated by endothelin, transforming growth factor(3, and reactive oxygen species, and finally lead to interstitial fibrosis and glomerulosclerosis observed in hypertension and diabetes. 

Membrane Signal Transduction Membrane Transport Protein Menaquinones-n Meniere s Disease Mesangial Cells... 

Kurogi Y, Miyata K, Okamura T, Hashimoto K, Tsutsumi K, Nasu M, Moriyasu M. Discovery of novel mesangial cell proliferation inhibitors using a three-dimensional database searching method. J Med Chem 2001 44 2304-7. 

In conclusion, ET is a polyfunctional cytokine that affects monocytes as well as vascular smooth muscle cells, anterior pituitary cells, and renal mesangial cells. In the biologic interface between ischemic or injured endothelium and monocytes, neutrophils, or lymphocytes, ET may play a significant role. 

Kiritoshi S, Nishikawa T, Sonoda K, Kukidome D, Senokuchi T, Matsuo T, Matsumura T, Tokunaga H, Brownlee M, Araki E (2003) Reactive oxygen species from mitochondria induce cyclooxygenase-2 gene expression in human mesangial cells potential role in diabetic nephropathy. Diabetes 52 2570-2577. 

S. E. Kasner and M. B. Ganz, Regulation of intracellular potassium in mesangial cells A fluorescence analysis using the dye, PI 11 1. Am. J. Physiol. 262, F462—F467 (1992). 

Similar observahons on the role of CDases were also obtained in rat renal mesangial cells shmulated with TNFa or nihic oxide donors. Both of these agonists were shown to stimulate sphingomyelinases, but only nitric oxide donors inhibited CDases and resulted in an increase in Cer levels and DNA fragmentahon (Huwiler et al., 1999). 

Huwiler, A., Pfeilschifter, J., and Van den Bosch, H., 1999, Nitric oxide donors induce stress signaling via ceramide formation in rat renal mesangial cells. J. Biol. Chem. 21 A. 7190-7195. 

Kester, M., Simonson, M. S., Mene, P., and Sedor, J. R., 1989, Interleukin-1 generates transmembrane signals from phospholipids through novel pathways in cultured rat mesangial cells. J. Clin. Invest. 83 718-723... 

Kitamura M, Suto T, Yokoo T, Shimizu F, Fine LG Transforming growth factor-(Jj is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells. J Immunol 1996 156 2964-2971. 

Jnng M, Lee HC, Ahn CW, Park W, Choi W, Kim H, Cho D, Lee GT, Li H-R. (2002) Effective isolation of magnesinm lithospermate B and its inhibition of aldose rednctase and fibronectin on mesangial cell line. Chem Pharm Bull 50 1135-1136. 

The renal glomerulus consists of endothelial cells, glomerular epithelial cells and mesangial cells. 

The mesangial cells of the glomerulus and the proximal tubular cells are the first choice targets for renal drug delivery. Both cell types play a central role in many disease processes in the kidney. 

Mesangial cells IgA (asialo) Anti- Thyl-Ab Rat Rat, man Renal fibrosis... 

Yokozawa, T., H. Oura, M. Hattori, M. Iwano, and K. Dohi. Effect of wen-pi-tang and its crude drug extracts on proliferation of cultured mouse mesangial cells. Phytother Res 1994 8(3) 170-173. 

Endothelins interact with several endocrine systems, increasing the secretion of renin, aldosterone, vasopressin, and ANP. They exert a variety of actions on the central and peripheral nervous systems, the gastrointestinal system, the liver, the urinary tract, the male and female reproductive systems, the eye, the skeletal system, and the skin. Finally, ET-1 is a potent mitogen for vascular smooth muscle cells, cardiac myocytes, and glomerular mesangial cells. 

Both the medulla and the cortex of the kidney synthesize prostaglandins, the medulla substantially more than the cortex. COX-1 is expressed mainly in cortical and medullary collecting ducts and mesangial cells, arteriolar endothelium, and epithelial cells of Bowman s capsule. COX-2 is restricted to the renal medullary interstitial cells, the macula densa, and the cortical thick ascending limb. 

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