TY - JOUR
T1 - Nitric-Oxide-Mediated Signaling in Podocyte Pathophysiology
AU - Semenikhina, Marharyta
AU - Stefanenko, Mariia
AU - Spires, Denisha R.
AU - Ilatovskaya, Daria V.
AU - Palygin, Oleg
N1 - Funding Information:
Funding: This research was funded by the National Institutes of Health grants R01 DK126720 (to O.P.), R01 HL148114 (to D.V.I.), and UL1TR001450/SCTR 2214 (to O.P.) and endowed funds from the SC SmartState Centers of Excellence (to O.P.) and the American Heart Association Postdoctoral Fellowship # 903584 (to D.R.S.).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/6
Y1 - 2022/6
N2 - Nitric oxide (NO) is a potent signaling molecule involved in many physiological and pathophysiological processes in the kidney. NO plays a complex role in glomerular ultrafiltration, vasodilation, and inflammation. Changes in NO bioavailability in pathophysiological conditions such as hypertension or diabetes may lead to podocyte damage, proteinuria, and rapid development of chronic kidney disease (CKD). Despite the extensive data highlighting essential functions of NO in health and pathology, related signaling in glomerular cells, particularly podocytes, is understudied. Several reports indicate that NO bioavailability in glomerular cells is decreased during the development of renal pathology, while restoring NO level can be beneficial for glomerular function. At the same time, the compromised activity of nitric oxide synthase (NOS) may provoke the formation of peroxynitrite and has been linked to autoimmune diseases such as systemic lupus erythematosus. It is known that the changes in the distribution of NO sources due to shifts in NOS subunits expression or modifications of NADPH oxidases activity may be linked to or promote the development of pathology. However, there is a lack of information about the detailed mechanisms describing the production and release of NO in the glomerular cells. The interaction of NO and other reactive oxygen species in podocytes and how NO-calcium crosstalk regulates glomerular cells’ function is still largely unknown. Here, we discuss recent reports describing signaling, synthesis, and known pathophysiological mechanisms mediated by the changes in NO homeostasis in the podocyte. The understanding and further investigation of these essential mechanisms in glomerular cells will facili-tate the design of novel strategies to prevent or manage health conditions that cause glomerular and kidney damage.
AB - Nitric oxide (NO) is a potent signaling molecule involved in many physiological and pathophysiological processes in the kidney. NO plays a complex role in glomerular ultrafiltration, vasodilation, and inflammation. Changes in NO bioavailability in pathophysiological conditions such as hypertension or diabetes may lead to podocyte damage, proteinuria, and rapid development of chronic kidney disease (CKD). Despite the extensive data highlighting essential functions of NO in health and pathology, related signaling in glomerular cells, particularly podocytes, is understudied. Several reports indicate that NO bioavailability in glomerular cells is decreased during the development of renal pathology, while restoring NO level can be beneficial for glomerular function. At the same time, the compromised activity of nitric oxide synthase (NOS) may provoke the formation of peroxynitrite and has been linked to autoimmune diseases such as systemic lupus erythematosus. It is known that the changes in the distribution of NO sources due to shifts in NOS subunits expression or modifications of NADPH oxidases activity may be linked to or promote the development of pathology. However, there is a lack of information about the detailed mechanisms describing the production and release of NO in the glomerular cells. The interaction of NO and other reactive oxygen species in podocytes and how NO-calcium crosstalk regulates glomerular cells’ function is still largely unknown. Here, we discuss recent reports describing signaling, synthesis, and known pathophysiological mechanisms mediated by the changes in NO homeostasis in the podocyte. The understanding and further investigation of these essential mechanisms in glomerular cells will facili-tate the design of novel strategies to prevent or manage health conditions that cause glomerular and kidney damage.
KW - glomerulus
KW - hypertension
KW - lupus nephritis
KW - nitric oxide synthase
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U2 - 10.3390/biom12060745
DO - 10.3390/biom12060745
M3 - Review article
C2 - 35740870
AN - SCOPUS:85130808282
SN - 2218-273X
VL - 12
JO - Biomolecules
JF - Biomolecules
IS - 6
M1 - 745
ER -