Expression of Dishevelled‐1 in wound healing after acute myocardial infarction: possible involvement in myofibroblast proliferation and migration

Abstract

One of our previous studies indicated that the expression of β‐catenin, which is the key factor of wnt‐frizzled pathway, increased significantly in the ischemic area of the rat heart 7 days after myocardial infarction (MI). Together with the results of other recent studies, we made an assumption that wnt‐frizzled pathway may be involved in the controlled cell proliferation and migration during repair processes after MI. To verify this assumption we tried to investigate the expression of another signal transduction molecule called Dishevelled in wnt‐frizzled pathway during the wound healing process after MI. The left descending coronary arteries of rats were ligated to induce MI. Immunohistochemistry SABC method and in situ hybridization were performed to detect the expression of Dishevelled‐1. The results showed, that one day after MI, Dishevelled‐1 mRNA but not protein expression was detected in the cells at the border zone of the infarction area; 4 days after MI the expression of Dishevelled‐1 increased exclusively and cytoplasmic Dishevelled‐1 was observed not only at the border zone but also in the infarct area; 7 days after MI, it seems that the expression reached its peak, the positive staining even spread into the endothelial and smooth muscle cells of the newly formed and pre‐existing blood vessels in the infarction area; after that the Dishevelled‐1 expression decreased abruptly and could hardly be detected 28 days after MI. Thus cytoplasmic Dishevelled‐1 may be involved in the controlled proliferation and migration of myofibroblasts and vascular endothelial cells, hence play a role during the wound healing process after MI.

The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart

“…Wound healing in myocardial infarct Regulation of β-catenin might be involved [107][108][109] Implicated in myofibroblast migration [104][105][106] …”

“…In a rat infarct model, Frizzled-2 is expressed in myofibroblasts that migrate into the infarcted area [104]. In addition, Dvl1 was detected in these myofibroblasts [105,106]. Interestingly, it has been reported that Dvl1 knock out mice may experience problems in infarct healing.…”

Smad1 Protects Cardiomyocytes From Ischemia-Reperfusion Injury

“…Members of the Wnt/fz signal transduction pathway are involved in cardiomyopathy and myocardial repair after myocardial infarction. 25,26 The role of the Wnt/fz pathway in programmed cell death is a matter of debate. 27,28 In physiological conditions, the level of ␤-catenin is regulated by Wnt signaling, which stabilizes cytosolic ␤-catenin.…”

Wnt Signaling and Injury Repair

“…Inhibition of Wnt signaling during skin wounding prevents formation of epithelial appendages including hair and sweat glands, which results in prominent scarring of the epidermis (Ito et al 2007). Myocardial infarctions in mammals produce a region of scar tissue surrounding the occluded vessels and if Wnt signaling is repressed, the scarring worsens and the result is myocardial rupture (Chen et al 2004).…”