Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury
Abstract
The amelioration of proteinuria resulting from inhibition of the renin-angiotensin pathway is thought to be predominantly caused by reduction in intraglomerular pressure. However, because studies have produced conflicting findings, whether podocyte-associated angiotensin II receptor signaling directly contributes to podocyte injury remains unclear. Angiotensin II receptor type 1 (AT1R) is internalized by clathrin- and dynamin-mediated endocytosis, and in this study the authors used podocyte-specific Dynamin 1 and 2 double-knockout mice to examine the effect of angiotensin II stimulation on AT1R in these double-knockout mice. Loss of AT1R internalization accentuated Rac1 activation and membrane ruffling in Dnm double-knockout podocytes. Podocyte-specific deletion of the receptor in Dnm double-knockout mice demonstrated improved albuminuria and kidney function and attenuation of membrane abnormalities—findings suggesting that podocyte-associated AT1R signaling augments podocyte injury.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 11, 2019
- Source ID
- 10.1681/asn.2019010053
Entities
People
- Christopher E. Pedigo
- Elizabeth Cross
- Heino Velazquez
- Hossam Hassan
- Jee-won Shin
- Kazunori Inoue
- Keita Soda
- Koichi Yamamoto
- Marwin Groener
- Peter Mundel
- Shuta Ishibe
- Wei Li
- Xuefei Tian
- Ying Wang
- Zhen Wang
Organizations
- Harvard Medical School
- National Institutes of Health
- Osaka Medical Research Foundation for Intractable Diseases
- Osaka University
- United States Department of Defense
- Yale School of Medicine