Renin is a crucial enzyme in the renin-angiotensin-aldosterone system (RAAS), which plays a significant role in regulating blood pressure and fluid balance in the body. The recombinant form of human renin is produced through genetic engineering techniques, allowing for its use in various research and therapeutic applications.
The RAAS is a hormone system that regulates blood pressure and fluid balance. When blood pressure is low, the kidneys release renin, which catalyzes the conversion of angiotensinogen (produced by the liver) into angiotensin I. Angiotensin I is then converted into angiotensin II by the angiotensin-converting enzyme (ACE) primarily in the lungs. Angiotensin II is a potent vasoconstrictor that increases blood pressure and stimulates the release of aldosterone from the adrenal glands, promoting sodium and water retention by the kidneys .
Renin is an aspartic protease enzyme that specifically cleaves angiotensinogen to produce angiotensin I. The human renin gene encodes a protein consisting of 406 amino acids. It is initially synthesized as a precursor, prorenin, which contains a 46 amino acid propeptide that inhibits its enzymatic activity. Prorenin is activated by proteolytic removal of this propeptide .
Recombinant human renin is produced using genetic engineering techniques. A cDNA encoding the full-length native human preprorenin is introduced into a suitable host cell line, such as HEK-293 cells. These cells are then cultured under specific conditions to express and secrete prorenin. The prorenin is purified from the conditioned medium and converted to active renin by removing the propeptide through trypsin digestion. Further purification steps, such as cation exchange and gel filtration chromatography, are employed to obtain highly pure active renin .
Recombinant human renin is used in various research and therapeutic applications: