Abstract
Renal glomerular diseases such as glomerulosclerosis and diabetic nephropathy often result in the loss of glomerular function and consequently end-stage renal disease. The glomerulus consists of endothelial cells, mesangial cells and glomerular epithelial cells also referred to as podocytes. A fine-tuned crosstalk between glomerular cells warrants control of growth factor synthesis and of matrix production and degradation, preserving glomerular structure and function. Hydrogen sulfide (H2S) belongs together with nitric oxide (NO) and carbon monoxide (CO) to the group of gasotransmitters. During the last three decades, these higher concentration toxic gases have been found to be produced in mammalian cells in a well-coordinated manner. Recently, it became evident that H2S and the other gasotransmitters share common targets as signalling devices that trigger mainly protective pathways. In several animal models, H2S has been demonstrated as a protective factor in the context of kidney disorders, in particular of diabetic nephropathy. Here, we focus on the synthesis and action of H2S in glomerular cells, its beneficial effects in the glomerulus and its action in the context of the other gaseous signalling molecules NO and CO.
Highlights
For quite a long time, H2 S was solely recognized as a smelly and toxic gas, causing fatal poisoning Fatal poisoning in the processing industry and in bathing accidents in lakes where the thermocline, which is the H2 S-containing layer, is near the surface
Glucocorticoids, immunosuppressive drugs or anti-inflammatory biologics are widely used. Based on these well-established therapeutic strategies, the administration of H2 S-releasing compounds or a regimen that forces the endogenous synthesis of H2 S would represent an additional approach to treat a variety of glomerular kidney diseases
Due to its ability to directly activate KATP [83] channels or to elevate cGMP levels by the inhibition of PDEs [78], H2 S acts as a powerful vasodilator (Figure 5)
Summary
For quite a long time, H2 S was solely recognized as a smelly and toxic gas, causing fatal poisoning Fatal poisoning in the processing industry and in bathing accidents in lakes where the thermocline, which is the H2 S-containing layer, is near the surface. A physiological role for H2 S was been demonstrated for the first time in 1996, when Hideo Kimura’s group showed that H2 S possesses physiological signalling properties as a neuromodulator [1] In this excellent research paper, Abe et al. As a consequence of diabetic glucose levels and other causes of glomerular injury, glomerular cells are affected by advanced glycation end products (AGEs), toxins, mechanical stress and reactive oxygen species (ROS) This stress situation interferes with the complex and fine-tuned intraglomerular crosstalk between mesangial cells, glomerular epithelial cells (podocytes) and glomerular endothelial cells resulting in a disturbance of glomerular integrity and function [3,4,5,6]. We briefly discuss the role of H2 S in glomerulopathies with a focus on the molecular mechanisms of production and action of this signalling mediator
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