Type 2 cGMP-dependent protein kinase regulates proliferation and differentiation in the colonic mucosa

American Journal of Physiology. Gastrointestinal and Liver Physiology
Rui WangDarren D Browning

Abstract

Signaling through cGMP has emerged as an important regulator of tissue homeostasis in the gastrointestinal tract, but the mechanism is not known. Type 2 cGMP-dependent protein kinase (PKG2) is a major cGMP effector in the gut epithelium, and the present studies have tested its importance in the regulation of proliferation and differentiation in the mouse colon and in colon cancer cell lines. Tissue homeostasis was examined in the proximal colon of Prkg2(-/-) mice using histological markers of proliferation and differentiation. The effect of ectopic PKG2 on proliferation and differentiation was tested in vitro using inducible colon cancer cell lines. PCR and luciferase reporter assays were used to determine the importance of Sox9 downstream of PKG2. The colons of Prkg2(-/-) mice exhibited crypt hyperplasia, increased epithelial apoptosis, and reduced numbers of differentiated goblet and enteroendocrine cells. Ectopic PKG2 was able to inhibit proliferation and induce Muc2 and CDX2 expression in colon cancer cells, but did not significantly affect cell death. PKG2 reduced Sox9 levels and signaling, suggesting possible involvement of this pathway downstream of cGMP in the colon. The work presented here demonstrates a novel antiprol...Continue Reading

References

Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·G M PitariS A Waldman
Mar 2, 2002·Science·Anna VelcichLeonard Augenlicht
Dec 6, 2002·The American Journal of Pathology·Kris A SteinbrecherMitchell B Cohen
Feb 1, 2003·Biochemical and Biophysical Research Communications·Hiroshi YamamotoYasuhito Yuasa
Feb 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·G M PitariS A Waldman
Nov 3, 2004·Pharmacology & Therapeutics·Leonard Ralph Forte
Jun 7, 2005·The Journal of Pharmacology and Experimental Therapeutics·Shiva KazerounianScott A Waldman
Nov 1, 2005·Cancer Letters·Yali HouDarren Browning
Dec 24, 2005·Physiological Reviews·F HofmannJ Schlossmann
Jul 13, 2006·Gastroenterology·Maria Van der SluisAlexandra W C Einerhand
Feb 14, 2008·Expert Opinion on Therapeutic Targets·Darren D Browning
Mar 8, 2008·Gastroenterology·David H ScovilleLinheng Li
Sep 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Malin E V JohanssonGunnar C Hansson
Nov 21, 2008·American Journal of Clinical Pathology·Bingjian LüMaode Lai
Dec 18, 2008·Handbook of Experimental Pharmacology·Franz HofmannPascal Weinmeister
Feb 18, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·M P Garin-LaflamM B Cohen
Feb 21, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Eric J FormeisterScott T Magness
Sep 10, 2009·Gastroenterology·Jieru Egeria LinScott Arthur Waldman
Dec 22, 2009·Current Molecular Pharmacology·P LiS A Waldman
Nov 26, 2010·Current Opinion in Gastroenterology·Kris A Steinbrecher, Mitchell B Cohen
Dec 4, 2010·Biochimica Et Biophysica Acta·Mehmet CoskunOle Haagen Nielsen
Jan 1, 2010·Future Medicinal Chemistry·Darren D BrowningRui Wang
May 11, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kris A SteinbrecherMitchell B Cohen
Jun 17, 2011·Nature·Jan Paul Medema, Louis Vermeulen
Jul 12, 2011·Trends in Molecular Medicine·Lars VereeckeGeert van Loo
Jul 27, 2011·Experimental Cell Research·Benjamin D Simons, Hans Clevers
Jan 31, 2012·Developmental Biology·Alexa HryniukDavid Lohnes

❮ Previous
Next ❯

Citations

Jun 2, 2016·Histochemistry and Cell Biology·Pauline T IkpaMarcel J C Bijvelds
Apr 28, 2017·PloS One·Sarah K SharmanDarren D Browning
Nov 13, 2013·The Journal of Biological Chemistry·Nirmalya BasuSandhya S Visweswariah
Dec 7, 2013·Current Opinion in Gastroenterology·Kris A Steinbrecher
Feb 20, 2014·Molecular Medicine Reports·Ying WangHai Qian
Nov 21, 2019·Biological Chemistry·Franz Hofmann
Aug 24, 2019·Small GTPases·Alemayehu A Gorfe, Kwang-Jin Cho
Aug 23, 2018·Frontiers in Oncology·Jeffrey A Rappaport, Scott A Waldman
Sep 19, 2020·Expert Review of Clinical Pharmacology·Jeffrey A Rappaport, Scott A Waldman
Jan 6, 2018·Cancer Prevention Research·Sarah K SharmanDarren D Browning
May 5, 2017·Cancer Prevention Research·Bianca N IslamDarren D Browning

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis