C-type natriuretic peptide inhibits rat mesangial cell proliferation by a phosphorylation-dependent mechanism |
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Authors: | K Segawa K Minami Nobuo Jimi Yasuhide Nakashima Akio Shigematsu |
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Institution: | (1) Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807, Japan, JP;(2) Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807, Japan, JP |
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Abstract: | We studied the effects of C-type natriuretic peptide (CNP) on rat cultured mesangial cell proliferation. (1) Exposure to
CNP (10 nM–1 μM for 72 h) inhibited 3H]thymidine incorporation into mesangial cells in a concentration-dependent manner. Atrial natriuretic peptide (1 nM–1 μM),
a peptide related to CNP, also decreased 3H]thymidine incorporation into these cells in a concentration-dependent manner. (2) Both CNP (10 nM-1 μM) and atrial natriuretic
peptide (10 nM-1 μM) also decreased mesangial cell number. (3) The cyclic GMP analog, 8-bromo-cyclic GMP (100 μM and 1 mM),
mimicked the inhibitory effects of CNP and atrial natriuretic peptide on 3H]thymidine incorporation into mesangial cells, whereas inhibitors of protein kinase C, protein kinase A, and protein kinase
G reduced the effect of both natriuretic peptides. Moreover, the phoshpatase inhibitor, calyculin A, increased 3H]thymidine incorporation into mesangial cells. (4) CNP and atrial natriuretic peptide decreased interleukin-1-, interleukin-6-,
platelet derived growth factor-, angiotensin II-induced 3H]thymidine incorporation into mesangial cells. These results suggest that CNP exerts inhibitory effects on mesangial cell
proliferation and that this effects depend on protein phosphorylation pathways.
Received: 17 March 1997 / Accepted: 29 August 1997 |
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Keywords: | C-type natriuretic peptide Protein kinase Mesangial cell Interleukin-1 Interleukin-6 Angiotensin II Platelet derived growth factor |
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