Most human cells have antennae-like projections called primary cilia that sprout from cell surfaces. These microscopic structures efficiently detect the mechano-biological fluid flow and its contents across cell surfaces in unicellular organisms.
But when they are defective in mammals, organ function is adversely affected, giving rise to several devastating genetic disorders or ciliopathies. Among them is polycystic kidney disease, which affects approximately 500,000 people in the United States.
New research from scientists at the Chapman University School of Pharmacy (CUSP) provides valuable insights into the mechanical inflammation that may be linked to defective primary cilia. Ashraf Mohieldin, Ph.D., a research associate at the Chapman University School of Pharmacy and the study’s principal investigator, led a team to examine and analyze the secretion characteristics of primary cilia — called extracellular vesicles, or EVs. Their findings were published in The Journal of Extracellular Vesicles.
Chief among those findings was the discovery of a new classification of ciliary EVs, which has a biomarker and unique features distinct from its counterparts (other EVs). Biomarkers may eventually lead to the development of diagnostic tests for related diseases.
In addition, these discoveries confirm previous research by Mohieldin’s team and others that EV secretion from primary cilia plays a role in cardiovascular regulation, including blood pressure, arrhythmias, heart failure and hypertrophy. It turns out that cilia release EVs to communicate with surrounding cells and organs in the body. The lack of such communication ability will interrupt various cellular processes, resulting in a ciliopathy disorder.
“These results will be important in improving our understanding of human genetic diseases, and for the first time, researchers will be able to selectively investigate the pathogenesis associated with this newly classified ciliary EV,” Mohieldin said.
In the future, Mohieldin’s team will use a translational animal model to develop a comprehensive understanding of the ciliary EV physiological role in patients with ciliopathy disease, utilizing the novel multimodal animal platforms, the latest generation ParaVision 6 software, and a newly purchased Magnetic Resonance Imaging (MRI) technology that enables safe studies with live animals and limits the number of animals used in this work.
Chapman has invested $2.5 million in the purchase of the MRI. Along with a recently expanded vivarium facility, Chapman and the School of Pharmacy are positioned to provide additional breakthroughs in biomedical translation research.
The work was supported in part by funding from the National Institutes of Health, American Heart Association and Chapman. Working together were Scripps Research scientists James J. Moresco and John R. Yates, supported by the National Institute of General Medical Sciences.
The published findings can be read in the Wiley Online Library.