Stimulation of Wnt/β-catenin signaling pathway with Wnt agonist reduces organ injury after hemorrhagic shock

The Journal of Trauma and Acute Care Surgery
Michael KuncewitchPing Wang

Abstract

Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need for effective therapy for hemorrhage patients. Wnt/β-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure of 30 mm Hg for 90 minutes, followed by resuscitation with crystalloid equal to two times the shed blood volume. After resuscitation, animals were infused with Wnt agonist (5 mg/kg) or vehicle (20% dimethyl sulfoxide in saline). Blood and tissue samples were collected 6 hours after resuscitation for analysis. Hemorrhagic shock increased serum levels of aspartate aminotransferase, lactate, and lactate dehydrogenase. Treatment with Wnt agonist significantly reduced these levels by 40%, 36%, and 77%, respectively. Wnt agonist also decreased blood urea ni...Continue Reading

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Citations

Nov 29, 2015·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Huizhi WangDavid A Scott
Feb 18, 2016·Expert Opinion on Therapeutic Targets·Jiali YangXiaoming Liu
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Feb 23, 2021·Frontiers in Cell and Developmental Biology·Imen JridiFrank J T Staal
Jul 21, 2021·Cell Biology and Toxicology·Dong-Hoon WonJun-Won Yun

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