Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

10 May 2016 - 16 May 2016
11 May 2016 - 13 May 2016

Imbalance in Molecular Signaling Pathways Leads to Arteriosclerosis

By BiotechDaily International staff writers
Posted on 30 May 2013
Print article
Image: Senior author Dr. Dwight A. Towler (Photo courtesy of Sanford-Burnham Medical Research Institute).
Image: Senior author Dr. Dwight A. Towler (Photo courtesy of Sanford-Burnham Medical Research Institute).
A recent paper described how an imbalance in expression of two genes contributes to development of cardiovascular disease by driving epithelial–mesenchymal transition (EMT) in cells lining the arteries, which cause them to calcify and harden, thereby increasing systolic blood pressure, and ultimately impairing distal blood flow.

EMT is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis, and in the initiation of metastasis for cancer progression.

Investigators at Sanford-Burnham Medical Research Institute (Orlando, FL, USA) studied the metabolic processes leading to arteriosclerosis by focusing on the interaction between the Dkk1 (dickkopf WNT signaling pathway inhibitor 1) and WNT7b (Wingless-type MMTV integration site family, member 7b) genes.

The Dkk1 gene encodes a protein that plays a key role in increasing the population of connective-tissue cells during wound repair, but prolonged Dkk1 signaling can lead to fibrosis and a stiffening of artery walls. WNT7b (Wingless-type MMTV integration site family, member 7b) is a member of a gene family consisting of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis.

The investigators reported in the May 16, 2013, online edition of the journal Arteriosclerosis, Thrombosis, and Vascular Biology that suppression of WNT7b signaling by Dkk1 enhanced EMT in aortic epithelial cells. This increased fibrotic mineralization of aortic epithelial cells through the accumulation of collagen and calcium. Inhibition of Dkk1 promoted WNT7b signaling, which prevented EMT and maintained the elastic morphology of the arterial wall epithelial cells.

"I think the strategy going forward is to find ways to modulate or inhibit Dkk1 function, but we are going to have to do it in a time-sensitive and cell type-specific fashion," said senior author Dr. Dwight A. Towler, professor of diabetes and obesity research at Sanford-Burnham Medical Research Institute. "In diseases such as chronic renal deficiency or diabetes, where unregulated Dkk1 signaling can be destructive, it may be appropriate to restrain the action of Dkk1 for a prolonged period of time."

Related Links:

Sanford-Burnham Medical Research Institute




Print article

Channels

Drug Discovery

view channel

Experimental Small-Molecule Anticancer Drug Blocks RAS-binding Domains

The experimental small-molecule anticancer drug rigosertib was shown to block tumor growth by acting as an RAS-mimetic and interacting with the RAS binding domains of RAF kinases, resulting in their inability to bind to RAS, which inhibited the RAS-RAF-MEK pathway. Oncogenic activation of RAS genes due to point mutations... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Lab Technologies

view channel

Huge Modifiable Biomedical Database to Be Available on the Wikidata Site

Genome researchers are exploiting the power of the open Internet community Wikipedia database to create a comprehensive resource for geneticists, molecular biologists, and other interested life scientists. While efficiency in generating scientific data improves almost daily, applying meaningful relationships between... Read more

Business

view channel

European Biotech Agreement to Promote Antigen-Drug Conjugation Technology

Two European biotech companies have joined forces to exploit and commercialize an innovative, site-specific ADC (antigen-drug conjugate) conjugation technology. ProBioGen (Berlin, Germany), a company specializing in the development and manufacture of complex glycoproteins and Eucodis Bioscience (Vienna, Austria), a... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.