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Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

Prasad, H and Mathew, JKK and Visweswariah, SS (2022) Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities. In: Frontiers in Endocrinology, 13 .

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Official URL: https://doi.org/10.3389/fendo.2022.911459


Receptor Guanylyl Cyclase C (GC-C) was initially characterized as an important regulator of intestinal fluid and ion homeostasis. Recent findings demonstrate that GC-C is also causally linked to intestinal inflammation, dysbiosis, and tumorigenesis. These advances have been fueled in part by identifying mutations or changes in gene expression in GC-C or its ligands, that disrupt the delicate balance of intracellular cGMP levels and are associated with a wide range of clinical phenotypes. In this review, we highlight aspects of the current knowledge of the GC-C signaling pathway in homeostasis and disease, emphasizing recent advances in the field. The review summarizes extra gastrointestinal functions for GC-C signaling, such as appetite control, energy expenditure, visceral nociception, and behavioral processes. Recent research has expanded the homeostatic role of GC-C and implicated it in regulating the ion-microbiome-immune axis, which acts as a mechanistic driver in inflammatory bowel disease. The development of transgenic and knockout mouse models allowed for in-depth studies of GC-C and its relationship to whole-animal physiology. A deeper understanding of the various aspects of GC-C biology and their relationships with pathologies such as inflammatory bowel disease, colorectal cancer, and obesity can be leveraged to devise novel therapeutics.

Item Type: Journal Article
Publication: Frontiers in Endocrinology
Publisher: Frontiers Media S.A.
Additional Information: The copyright for this article belongs to the Authors.
Keywords: cyclic GMP; cyclic GMP phosphodiesterase; cyclic nucleotide gated channel; cystic fibrosis transmembrane conductance regulator; guanylate cyclase; guanylin; ligand; membrane protein; natriuretic factor; receptor guanylyl cyclase c; unclassified drug; uroguanylin, adipose tissue; bile secretion; brain-gut axis; carcinogenesis; cell membrane; colon cancer; colorectal cancer; digestive function; diuresis; drug delivery system; dysbiosis; energy expenditure; enteritis; enteroendocrine cell; enteropathy; enzyme activity; Escherichia coli; food intake; gastrointestinal motility; gastrointestinal tract function; gene expression; gene mutation; goblet cell; health; homeostasis; human; immune response; inflammation; inflammatory bowel disease; insulin release; lipolysis; liver regeneration; liver toxicity; metastatic colorectal cancer; natriuresis; nephrotic syndrome; nociception; non insulin dependent diabetes mellitus; obesity; pancreas cancer; Paneth cell; phenotype; phosphorylation; protein function; Review; signal transduction; stomach cancer; structure analysis; synergistic effect; therapeutic research; thermogenesis
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 04 Aug 2022 09:58
Last Modified: 04 Aug 2022 09:58
URI: https://eprints.iisc.ac.in/id/eprint/75329

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