Prostasin: An Epithelial Sodium Channel Regulator

Abstract

Prostasin is a glycophosphatidylinositol-anchored protein which is found in prostate gland, kidney, bronchi, colon, liver, lung, pancreas, and salivary glands. It is a serine protease with trypsin-like substrate specificity which was first purified from seminal fluid in 1994. In the last decade, its diverse roles in various biological and physiological processes have been elucidated. Many studies done to date suggest that prostasin is one of several membrane peptidases regulating epithelial sodium channels in mammals. A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature and the National Library of Medicine. The data was also assessed from journals and books that published relevant articles in this field. Understanding the mechanism by which prostasin and its inhibitors regulate sodium channels has provided a new insight into the treatment of hypertension and some other diseases like cystic fibrosis. Prostasin plays an important role in epidermal growth factor receptor (EGFR) signal modulation. Extracellular proteases have been implicated in tumor metastasis and local tissue invasion because of their ability to degrade extracellular matrices.

Prostasin, proteases, and preeclampsia

“…The authors provide evidence for prostasin as a relevant molecule to preeclampsia, in keeping with previous data where its increase has been related to abnormal placental development in a mouse model [16] and kidney dysfunction, and hypertension in humans [11]. Prostasin has been shown to be upregulated by aldosterone and can be negatively regulated by protease inhibitors HA-1, HA-2, or nexin-1.…”

“…They catalyse the cleavage of other proteins dependent upon the presence of the nucleophilic serine residue in the enzyme's active site. They are functionally diverse and play important roles in a number of central physiological processes, including digestion, blood clotting, and immunity [11]. Research into the role of serine proteases in preeclampsia is a promising new field with targets, such as corin [12], chymase [13], and serine protease high-temperature requirement factor A4 [14] shown to be increased in the disease.…”

Prostasin and hepatocyte growth factor B in factor VIIa generation: Serine protease knockdowns in zebrafish

“…Reportedly, prostasin, which contains a catalytically active site, has been shown to regulate epithelial cell sodium channels and modulate epidermal growth factor receptor signaling. 22 Its soluble form is present in seminal fluid. It is also expressed in the liver, where FVII is synthesized.…”

“…It is probable that, in addition to their role in Fviia generation, they may also be partially affecting Fvii levels via an unknown mechanism. Reportedly, prostasin, which contains a catalytically active site, has been shown to regulate epithelial cell sodium channels and modulate epidermal growth factor receptor signaling 22 . Its soluble form is present in seminal fluid.…”

Genetic polymorphism of the prostasin gene in hypertensive pregnant Pakistani females

“… 8 In a population of Xinjiang Kazakh, Fang et al identified the correlation of genetic variants in prostasin gene with essential hypertension, but significant association was observed only with E342K in the hypertensive patients. 9 Variations in findings from many studies indicate the presence of racial disparities in prostasin polymorphism and suggest the need for further research in other ethnicities with a larger sample size. No study to date has explored the role of prostasin gene mutation in Pakistani hypertensive patients.…”