June 21, 2019 | Jola Glotzer
Piezo1 and lung edema
Three CBC Award recipients, Yulia Komarova, Asrar Malik and Jalees Rehman, UIC, co-authored a recent PNAS publication describing a pressure-sensing protein that may be involved in causing pulmonary edema
Congratulations to Yulia Komarova, Asrar Malik and Jalees Rehman, UIC, and co-authors on a recent publication in PNAS, “Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions.”
The researchers queried whether piezo 1, a protein with mechanical pressure-sensing properties and expressed in the endothelial cells lining blood vessels, was involved in loosening the inter-cellular junctions thus allowing fluid leakage to the lungs causing pulmonary edema. Data from an animal model confirmed their hypothesis. “Our experiments suggest that by either blocking the activity of piezo 1 or by bolstering the adherens junctions we can prevent fluid from entering the lungs,” Komarova said. “Small drug molecules that achieve these goals could represent novel therapeutic approaches to treat lung edema associated with heart failure.”
Komarova, Malik and Rehman are all CBC Awardees: Komarowa received a recent (2018) Accelerator Award; Malik and two postdocs in his lab, Jeffrey Klomp and Kit Man Tsang, received Postdoctoral Research Awards (2016 and 2014, respectively), and Rehman received a Catalyst Award (2009). In addition, in 2014, Malik co-organized and presented his research at the CBC Vascular Biology Exploratory Workshop (see below for the details).
Researchers reveal key role of pressure-sensing protein in lung edema
UIC today | by Sharon Parmet | June 11, 2019
CBC Awardees Yulia Komarova, Asrar Malik and Jalees Rehman, UIC, are co-authors on the PNAS publication.
Researchers at the University of Illinois at Chicago describe for the first time the role of a unique, pressure-sensing protein in the development of lung edema — a condition in which chronic high vascular pressure in the lungs causes fluid from the bloodstream to enter the air spaces of the lungs.
The results, which are published in the Proceedings of the National Academy of Sciences, suggest that suppressing the activity of the protein could be a new approach to treating lung edema.
Lung edema can have a variety of causes, including heart failure. Certain types of heart failure — where the heart is chronically unable to pump blood efficiently — can cause increased pressure in the blood vessels in the lungs. The high pressure can result in capillary stress failure, where connections between the individual cells that make up the walls of the capillary blood vessels become looser, allowing fluid from the bloodstream to enter the air spaces in the lungs.
Yulia Komarova, UIC associate professor of pharmacology, and Asrar Malik, Schweppe Family Distinguished Professor and head of pharmacology in the UIC College of Medicine, have been studying adherens junctions — the structures that bind together the cells that make up blood vessels. Adherens junctions act like adjustable nuts and bolts that can be tightened or loosened to modulate the flow of fluids and blood cells into and out of the bloodstream, such as immune cells that travel in the blood to get to areas where they are needed.
Komarova and colleagues wanted to see if a protein called piezo 1 — which is found in many cell types, including in the endothelial cells that line the blood vessels, and that can sense mechanical pressure — was involved in triggering adherens junctions to loosen up under conditions of high fluid pressure in the lungs.
The researchers engineered mice where piezo 1 was deleted in the adult animal in the endothelial cells. They then elevated the pressure in blood vessels in the lungs in order to mimic the effects of heart failure. In mice where piezo 1 was deleted in the endothelial cells, minimal fluid was seen entering the lungs, while in mice that had the piezo 1 protein, the lungs filled with fluid as blood pressure increased.
In a separate experiment, Komarova and colleagues used a mouse model where the adherens junctions were artificially reinforced in endothelial cells to keep the connections between individual cells lining the blood vessel cells tight. In these mice, no fluid was seen to enter the lungs when high pressures were induced in the animals even when they had the piezo 1 protein.
“Our experiments suggest that by either blocking the activity of piezo 1 or by bolstering the adherens junctions we can prevent fluid from entering the lungs,” Komarova said. “Small drug molecules that achieve these goals could represent novel therapeutic approaches to treat lung edema associated with heart failure.”
Emily Friedrich, Zhigang Hong, Shiqin Xiong, Ming Zhong, Anke Di, Jalees Rehman are co-authors on the paper.
This research was supported by grants T32HL007829 and R01HL045638 from the National Institutes of Health.
Source:
Adapted (with modifications) from UIC today, by Sharon Parmet, published on June 11, 2019.
Citation:
Friedrich EE, Hong Z, Xiong S, Zhong M, Di A, Rehman J, Komarova YA, Malik AB. Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions. Proc Natl Acad Sci U S A. 2019 Jun 11. [Epub ahead of print] (PubMed)
Featured CBC Community member(s):
Yulia Komarova, UIC
- CBC Accelerator Award (2018):
PI: Yulia Komarova (UIC) for the project:
▸ Development of a novel treatment for age-related macular degeneration (AMD)
Asrar Malik, UIC
- CBC Postdoctoral Research Award (2016):
▸ Mapping the Transcriptional Landscape of Hypoxic Endothelial Cells
PIs: Jeffrey Klomp (postdoc) and Asrar B. Malik (UIC) - CBC Postdoctoral Research Award (2014):
▸ CRISPR-Based Screening to Identify The Genetic Control of Hypoxia in Vascular Differentiation
PIs: Kit Man Tsang (postdoc) and Asrar B. Malik (UIC) - CBC Exploratory Workshop (2014):
▸ The CBC Vascular Biology Exploratory Workshop
Asrar B. Malik (UIC) — Workshop Organizer and Speaker
Jalees Rehman, UIC
- CBC Catalyst Award (2009):
▸ Oxygen Sensing in Endothelial Progenitor Cells
PIs: David Eddington and Jalees Rehman (UIC), and Navdeep Chandel (NU)
ARTICLES PUBLISHED IN THE PAST ABOUT THE FEATURED CBC COMMUNITY MEMBER(S):
May 23, 2019 (Updated June 12, 2019)
Success Story
▸ Endothelial barrier—tight then leaky
Three CBC affiliates — Andrei Karginov and Asrar B. Malik (UIC), and Teng-Leong Chew (Janelia) — contribute to a new study in Cell Chemical Biology about the endothelial barrier regulation
April 10, 2018
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▸ Understanding the pathogenesis of atrial fibrillation (AFib) in the Latino population — a CBC Awardee, Jalees Rehman, UIC, contributes to the story
July 2, 2018
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▸ TWIK-ing inflammation
Two UIC scientists with links to CBC, Asrar Malik and Jalees Rehman, identify a new potassium channel crucial for activating inflammation
October 5, 2018
News
▸ Inaugural Accelerator Awards Announced!
1st Application Round (Spring 2018)
April 27, 2018
Success Story
▸ UIC scientist with ties to CBC, Yulia Komarova, contributes to a study on how human cytomegalovirus (HCMV) hijacks microtubules to form an intracellular virus maturation compartment
October 16, 2017
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▸ Three UIC scientists with links to CBC contribute to our understanding of “explosive” cell death—pyroptosis—in lung infections
December 21, 2016
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▸ New Technique Switches Key Biomolecules “on” and “off”