caa a22 4500 606234810 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2528-6 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2528-6 Dexamethasone-dependent modulation of cyclic GMP synthesis in podocytes [Elektronische Daten] [Barbara Lewko, Anna Waszkiewicz, Anna Maryn, Magdalena Gołos, Elżbieta Latawiec, Agnieszka Daca, Jacek Witkowski, Stefan Angielski, Jan Stępiński] Podocytes may be direct target for glucocorticoid therapy in glomerular proteinuric disease. Permeability of podocytes largely depends on their capacity to migrate which involves the contractile apparatus in their foot processes. In this study, we examined the effect of synthetic glucocorticoid dexamethasone (DEX) on the ability of podocytes to produce cyclic guanosine monophosphate (cGMP) in the presence of vasoactive factors, atrial natriuretic peptide (ANP), nitric oxide (NO), and angiotensin II (Ang II). We investigated also the effects of cGMP and DEX on podocyte motility. Primary rat podocytes and immortalized mouse podocytes were pretreated with 1µM DEX for 4 or 24h. Glomerular hypertension was mimicked by subjecting the cells to mechanical stress. Total and subcellular cGMP levels were determined in podocytes incubated with 0.1µM ANP, 1µM S-nitroso-N-acetyl penicillamine (SNAP), and 1µM Ang II. Cell motility was estimated by a wound-healing assay. The ANP-dependent production of cGMP increased after 4h exposition to DEX, but was attenuated after 24h. Adversely, a 24-h pretreatment with DEX augmented the NO-dependent cGMP synthesis. Ang II suppressed the ANP-dependent cGMP production and the effect was enhanced by DEX in mechanical stress conditions. Mechanical stress reduced total cGMP production in the presence of all stimulators, whereas extracellular to total cGMP ratio increased. 8-Br cGMP enhanced podocyte migration which was accompanied by F-actin disassembly. In the presence of DEX these effects were prevented. We conclude that DEX modulates the production of cGMP in podocytes stimulated with vasoactive factors such as Ang II, ANP, and NO, and the effect is time-dependent. cGMP increases podocyte motility, which is prevented by DEX. This mechanism may account for the antiproteinuric effect of glucocorticoids. The Author(s), 2015 Podocytes nationallicence Dexamethasone nationallicence cGMP nationallicence Angiotensin II nationallicence Mechanical stress nationallicence Motility nationallicence Lewko Barbara Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut Waszkiewicz Anna Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut Maryn Anna Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut Gołos Magdalena Department of Immunopathology, Medical University of Gdansk, Gdansk, Poland aut Latawiec Elżbieta Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut Daca Agnieszka Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdansk, Poland aut Witkowski Jacek Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland aut Angielski Stefan Laboratory of Cellular and Molecular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw/Gdansk, Poland aut Stępiński Jan Laboratory of Cellular and Molecular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw/Gdansk, Poland aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 243-253 0300-8177 409:1-2<243 2015 409 11010 https://doi.org/10.1007/s11010-015-2528-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2528-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lewko Barbara Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut NATIONALLICENCE 700 1- Waszkiewicz Anna Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut NATIONALLICENCE 700 1- Maryn Anna Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut NATIONALLICENCE 700 1- Gołos Magdalena Department of Immunopathology, Medical University of Gdansk, Gdansk, Poland aut NATIONALLICENCE 700 1- Latawiec Elżbieta Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland aut NATIONALLICENCE 700 1- Daca Agnieszka Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdansk, Poland aut NATIONALLICENCE 700 1- Witkowski Jacek Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland aut NATIONALLICENCE 700 1- Angielski Stefan Laboratory of Cellular and Molecular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw/Gdansk, Poland aut NATIONALLICENCE 700 1- Stępiński Jan Laboratory of Cellular and Molecular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw/Gdansk, Poland aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 243-253 0300-8177 409:1-2<243 2015 409 11010