The role of cGMP and its signaling pathways in kidney disease

Shen, Kunyu, Johnson, David W. and Gobe, Glenda C. (2016) The role of cGMP and its signaling pathways in kidney disease. AJP - Renal Physiology, 311 4: F671-F681. doi:10.1152/ajprenal.00042.2016

Author Shen, Kunyu
Johnson, David W.
Gobe, Glenda C.
Title The role of cGMP and its signaling pathways in kidney disease
Journal name AJP - Renal Physiology   Check publisher's open access policy
ISSN 1522-1466
Publication date 2016-10-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1152/ajprenal.00042.2016
Open Access Status Not yet assessed
Volume 311
Issue 4
Start page F671
End page F681
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Subject 1314 Physiology
2748 Urology
Abstract Cyclic nucleotide signal transduction pathways are an emerging research field in kidney disease. Activated cell surface receptors transduce their signals via intracellular second messengers such as cAMP and cGMP. There is increasing evidence that regulation of the cGMP-cGMP-dependent protein kinase 1-phosphodiesterase (cGMP-cGK1-PDE) signaling pathway may be renoprotective. Selective PDE5 inhibitors have shown potential in treating kidney fibrosis in patients with chronic kidney disease (CKD), via their downstream signaling, and these inhibitors also have known activity as antithrombotic and anticancer agents. This review gives an outline of the cGMP-cGK1-PDE signaling pathways and details the downstream signaling and regulatory functions that are modulated by cGK1 and PDE inhibitors with regard to antifibrotic, antithrombotic, and antitumor activity. Current evidence that supports the renoprotective effects of regulating cGMP-cGK1-PDE signaling is also summarized. Finally, the effects of icariin, a natural plant extract with PDE5 inhibitory function, are discussed. We conclude that regulation of cGMP-cGK1-PDE signaling might provide novel, therapeutic strategies for the worsening global public health problem of CKD.
Keyword CGK1
CGMP kinase 1
Kidney disease
Phosphodiesterase inhibitors
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
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