Smooth muscle actin as a novel serologic marker of severe intestinal damage in rat intestinal ischemia–reperfusion and human necrotising enterocolitis

Intestinal ischemia-reperfusion injury (i-IRI) is a rare disorder with a high mortality rate, resulting from the loss of blood flow to an intestinal segment. Most of the damage is triggered by the restoration of flow and the arrival of cytokines and reactive oxygen species (ROS), among others. Inactivation of these molecules before tissue reperfusion could reduce intestinal damage. The aim of this work was to analyze the preventive effect of allopurinol and nitroindazole on intestinal mucosal damage after i-IRI. Wag/RijHsd rats were subjected to i-IRI by clamping the superior mesenteric artery (for 1 or 2 h) followed by a 30 min period of reperfusion. Histopathological intestinal damage (HID) was assessed by microscopic examination of histological sections obtained from injured intestine. HID was increased by almost 20% by doubling the ischemia time (from 1 to 2 h). Nitroindazole reduced HID in both the 1 and 2 h period of ischemia by approximately 30% and 60%, respectively (p < 0.001). Our preliminary results demonstrate that nitroindazole has a preventive/protective effect against tissue damage in the early stages of i-IRI. However, to better understand the molecular mechanisms underlying this phenomenon, further studies are needed.

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Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia–reperfusion injury in a rat

Pediatric Surgery International ◽

10.1007/s00383-016-3979-x ◽

2016 ◽

Vol 32 (12) ◽

pp. 1193-1200 ◽

Cited By ~ 6

Author(s):

I. Sukhotnik ◽

N. Nissimov ◽

Y. Ben Shahar ◽

D. Moati ◽

N. Bitterman ◽

...

Keyword(s):

Reperfusion Injury ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intestinal Damage ◽

Intestinal Ischemia Reperfusion

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p21waf1/cip1/sdi1 as a Central Regulator of Inducible Smooth Muscle Actin Expression and Differentiation of Cardiac Fibroblasts to Myofibroblasts

Molecular Biology of the Cell ◽

10.1091/mbc.e07-03-0270 ◽

2007 ◽

Vol 18 (12) ◽

pp. 4837-4846 ◽

Cited By ~ 32

Author(s):

Sashwati Roy ◽

Savita Khanna ◽

Trenton Rink ◽

Jared Radtke ◽

W. Taylor Williams ◽

...

Keyword(s):

Smooth Muscle ◽

Molecular Mechanisms ◽

Cardiac Fibroblasts ◽

Smooth Muscle Actin ◽

Ischemia Reperfusion ◽

Boundary Region ◽

Muscle Actin ◽

Phenotypic Switch ◽

Infarct Region

The phenotypic switch of cardiac fibroblasts (CFs) to myofibroblasts is essential for normal and pathological wound healing. Relative hyperoxic challenge during reoxygenation causes myocardial remodeling. Here, we sought to characterize the novel O2-sensitive molecular mechanisms responsible for triggering the differentiation of CFs to myofibroblasts. Exposure of CFs to hyperoxic challenge–induced transcription of smooth muscle actin (SMA) and enhanced the stability of both Acta2 transcript as well as of SMA protein. Both p21 deficiency as well as knockdown blunted hyperoxia-induced Acta2 and SMA response. Strikingly, overexpression of p21 alone markedly induced differentiation of CFs under normoxia. Overexpression of p21 alone induced SMA transcription by down-regulating YB1 and independent of TGFβ1. In vivo, hyperoxic challenge induced p21-dependent differentiation of CFs to myofibroblasts in the infarct boundary region of ischemia-reperfused heart. Tissue elements were laser-captured from infarct boundary and from a noninfarct region 0.5 mm away. Reperfusion caused marked p21 induction in the infarct region. Acta2 as well as SMA expression were markedly up-regulated in CF-rich infarct boundary region. Of note, ischemia-reperfusion–induced up-regulation of Acta2 in the infarct region was completely abrogated in p21-deficient mice. This observation establishes p21 as a central regulator of reperfusion-induced phenotypic switch of CFs to myofibroblasts.

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