Journal
CURRENT HYPERTENSION REPORTS
Volume 22, Issue 4, Pages -Publisher
SPRINGER
DOI: 10.1007/s11906-020-01037-1
Keywords
Megalin; V-ATPase; Chloride channel; Renin; Prorenin; Angiotensinogen; Proteinuria
Categories
Funding
- National Natural Science Foundation of China [81800383, 81870605]
- Shenzhen Key Laboratory of Metabolism and Cardiovascular Homeostasis
- Shenzhen Municipal Science and Technology Innovation Council [JCYJ20160307160819191]
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Purpose of Review Megalin is well known for its role in the reabsorption of proteins from the ultrafiltrate. Recent studies suggest that megalin also reabsorbs renin and angiotensinogen. Indeed, without megalin urinary renin and angiotensinogen levels massively increase, and even prorenin becomes detectable in urine. Recent Findings Intriguingly, megalin might also contribute to renal angiotensin production, as evidenced from studies in megalin knockout mice. This review discusses these topics critically, concluding that urinary renin-angiotensin system components reflect diminished reabsorption rather than release from renal tissue sites and that alterations in renal renin levels or megalin-dependent signaling need to be ruled out before concluding that angiotensin production at renal tissue sites is truly megalin dependent. Future studies should evaluate megalin-mediated renin/angiotensinogen transcytosis (allowing interstitial angiotensin generation), and determine whether megalin prefers prorenin over renin, thus explaining why urine normally contains no prorenin.
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