EDITOR'S PICK: To contract or not to contract: decision controlled by two microRNAs
The walls of blood vessels contain muscle cells known as vascular smooth muscle cells (VSMCs). These cells contract and relax to modulate blood pressure and distribute blood to the areas of the body that need it most. However, some environmental signals, many of which are associated with human disease, cause VSMCs to switch from being contractile in nature to being dividing cells that produce large amounts of the proteins that form tissue matrix. Despite the fact that this switch has been associated with a number of human blood vessel diseases, the mechanisms that control it have not been well defined. However, a team of researchers at the Max-Planck-Institut für Herz- und Lungenforschung, Germany, has now identified two small RNA molecules (microRNAs) known miR-143 and miR-145 that regulate acquisition and/or maintenance of the contractile nature of VSMCs in mice.
The team, led by Thomas Braun and Thomas Boettger, generated mice lacking both miR-143 and miR-145 and found that they had dramatically reduced numbers of contractile VSMCs and increased numbers of tissue matrix–producing VSMCs in their large arterial blood vessels. Further analysis revealed that these two small RNA molecules were required for normal contractility of arteries in vitro and maintenance of normal blood pressure in vivo. As their absence led to signs of blood vessel disease in mice, the authors suggest that miR-143/145 might provide new therapeutic targets to enhance blood vessel repair and attenuate blood vessel disease.
In an accompanying commentary, Michael Parmacek, at the University of Pennsylvania School of Medicine, Philadelphia, discusses the importance of this study and highlights the fact that miR-143 and miR-145 were found to alter the expression of differing sets of genes, meaning that future studies will need to determine precisely how they alter control of blood pressure and disease development.
TITLE: Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster
AUTHOR CONTACT:
Thomas Braun
Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim, Germany.
Phone: 49-6032-705-401; Fax: 49-6032-705-419; E-mail: thomas.braun@kerckhoff.mpg.de.
Thomas Boettger
Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim, Germany.
Phone: 49-6032-705-401; Fax: 49-6032-705-419; E-mail: thomas.boettger@mpi-bn.mpg.de.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38864
ACCOMPANYING COMMENTARY
TITLE: MicroRNA-modulated targeting of vascular smooth muscle cells
AUTHOR CONTACT:
Michael S. Parmacek
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: 215-662-3140; Fax: 215-349-8017; Email: michael.parmacek@uphs.upenn.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=40503
EDITOR'S PICK: Cellular crosstalk linked to lung disease
Crosstalk between cells lining the lung (epithelial cells) and airway smooth muscle cells is important in lung development. However, it has also been shown to contribute to several lung diseases, including asthma and pulmonary hypertension. A team of researchers, at the University of Pennsylvania, Philadelphia, has now molecularly characterized one crosstalk pathway in mice, providing potential new therapeutic targets for treating individuals with lung diseases, such as asthma and pulmonary hypertension, which are caused, at least in part, by affects on airway smooth muscle cells.
The team, led by Edward Morrisey and Ethan David Cohen, used numerous in vivo gain- and loss-of-function approaches to demonstrate that a Wnt7b/Tnc/Pdgfr crosstalk pathway was important for mouse smooth muscle development, with Wnt7b being exclusively expressed by lung epithelial cells and Pdgfr being expressed by the developing airway smooth muscle cells. Importantly, expression of the components of this crosstalk pathway was upregulated in a mouse model of asthma and humans with pulmonary hypertension, thereby indentifying the Wnt/Tnc/Pdgfr crosstalk pathway as important in both lung development and adult lung disease.
TITLE: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway
AUTHOR CONTACT:
Edward E. Morrisey
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-3010; Fax: (215) 573-2094; E-mail: emorrise@mail.med.upenn.edu.
Ethan David Cohen
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-3010; Fax: (215) 573-2094; E-mail: cohene@mail.med.upenn.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38079
ONCOLOGY: Two gene defects work together to increase cancer susceptibility
TITLE: Deficiencies in Chfr and Mlh1 synergistically enhance tumor susceptibility in mice
AUTHOR CONTACT:
Donald James Tindall
Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Phone: (507) 284-8139; Fax: (507) 284-2384; E-mail: tindall.donald@mayo.edu.
Junjie Chen
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Phone: (713) 792-4863; Fax: (713) 794-5369; E-mail: jchen8@mdanderson.org.
Zheng Fu
Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Phone: (507) 284-8138; Fax: (507) 284-2384; E-mail: fu.zheng@mayo.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=37405
ONCOLOGY: Keeping it in the family: EGFR/ERBB family member ERBB3 a new target for colorectal cancer?
TITLE: Tumor-specific apoptosis caused by deletion of the ERBB3 pseudo-kinase in mouse intestinal epithelium
AUTHOR CONTACT:
David W. Threadgill
University of North Carolina, Chapel Hill, North Carolina, USA.
Phone: (919) 515-2292; Fax: (919) 515-3355; E-mail: threadgill@ncsu.edu.
Daekee Lee
Ewha Womans University, Seoul, Republic of Korea.
Phone: 82-2-3277-4368; Fax: 82-2-3277-3760; E-mail: daekee@ewha.ac.kr.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36435
NEPHROLOGY: SGK1 and WNK4: more links in the chain between the hormone aldosterone and the ion channel NCC
TITLE: Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway
AUTHOR CONTACT:
David J. Rozansky
Oregon Health and Science University, Portland, Oregon, USA.
Phone: (503) 494-8081; Fax: (503) 418-6718; E-mail: rozansky@ohsu.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38323
Journal
Journal of Clinical Investigation