Proinsulin C-peptide prevents hyperglycemia-induced vascular leakage and metastasis of melanoma cells in the lungs of diabetic mice

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Hye-Yoon JeonKwon-Soo Ha

Abstract

C-peptide has a beneficial effect against diabetic complications, but its role in hyperglycemia-induced metastasis is unknown. We investigated hyperglycemia-mediated pulmonary vascular leakage and metastasis and C-peptide inhibition of these molecular events using human pulmonary microvascular endothelial cells (HPMVECs) and streptozotocin-induced diabetic mice. VEGF, which is elevated in the lungs of diabetic mice, activated transglutaminase 2 (TGase2) in HPMVECs by sequential elevation of intracellular Ca2+ and reactive oxygen species (ROS) levels. VEGF also induced vascular endothelial (VE)-cadherin disruption and increased the permeability of endothelial cells, both of which were prevented by the TGase inhibitors monodansylcadaverine and cystamine or TGM2-specific small interfering RNA. C-peptide prevented VEGF-induced VE-cadherin disruption and endothelial cell permeability through inhibiting ROS-mediated activation of TGase2. C-peptide supplementation inhibited hyperglycemia-induced ROS generation and TGase2 activation and prevented vascular leakage and metastasis in the lungs of diabetic mice. The role of TGase2 in hyperglycemia-induced pulmonary vascular leakage and metastasis was further demonstrated in diabetic Tgm2-/...Continue Reading

References

Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·David C SaneCharles S Greenberg
Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·Qingmin Ruan, Gail V W Johnson
Apr 6, 2007·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Samuel J WangCharles R Thomas
Apr 19, 2007·Nature Reviews. Genetics·Don X Nguyen, Joan Massagué
Apr 2, 2010·American Journal of Nephrology·Claire E HillsPaul E Squires
Apr 20, 2010·Cardiovascular Research·David O Bates
Feb 14, 2012·Autoimmunity Reviews·Antonio Di SabatinoGino Roberto Corazza
Mar 24, 2012·Diabetes·John WahrenAnders A F Sima
Oct 3, 2012·Cold Spring Harbor Perspectives in Medicine·Kellen L Meadows, Herbert I Hurwitz
Dec 15, 2012·Critical Reviews in Oncogenesis·Thomas N Seyfried, Leanne C Huysentruyt
Jan 8, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Mi Kyung ParkChang Hoon Lee
Oct 22, 2013·Cardiovascular Research·Young-Cheol LimKwon-Soo Ha
Nov 23, 2013·Nature Reviews. Cancer·Nicolas ReymondAnne J Ridley
Jul 10, 2014·The Journal of Investigative Dermatology·Young-Cheol LimKwon-Soo Ha
Sep 23, 2014·Cardiovascular Research·Mahendra Prasad BhattKwon-Soo Ha
Feb 4, 2016·Asian Pacific Journal of Cancer Prevention : APJCP·Kutan OzerEmin Ozbek
Feb 18, 2016·Diabetes Care·John WahrenJoseph C Arezzo
Jul 20, 2016·Oxidative Medicine and Cellular Longevity·Wei LiQingyong Ma
Aug 25, 2016·The Journal of Endocrinology·Mahendra Prasad BhattKwon-Soo Ha
Feb 23, 2017·World Journal of Surgical Oncology·Malte KrönigCordula Annette Jilg
Mar 21, 2017·Oncogenesis·A Vasconcelos-Dos-SantosA R Todeschini
Jul 29, 2017·The Journal of Endocrinology·Yeon-Ju LeeKwon-Soo Ha

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Citations

May 7, 2019·The Journal of Clinical Endocrinology and Metabolism·William HellströmChatarina Löfqvist
Aug 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jee-Yeon LeeKwon-Soo Ha
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Sana Abdul KhaliqMee-Sup Yoon

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