title: Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy.
abstract: The intrarenal renin-angiotensin system plays a crucial role in the regulation of renal circulation and sodium reabsorption through the activation of vascular, glomerular, and tubular angiotensin II type 1 (AT(1)) receptor signaling. We previously cloned a molecule that specifically interacted with the murine AT(1) receptor to inhibit AT(1) receptor signaling, which we named ATRAP (for AT(1) receptor-associated protein). Since murine ATRAP was shown to be highly expressed in the kidney, in the present study we investigated expression and distribution of human ATRAP in normal kidney and renal biopsy specimens from patients with IgA nephropathy. In the normal human kidney, both ATRAP mRNA and protein were widely and abundantly distributed along the renal tubules from Bowman's capsule to the medullary collecting ducts. In all renal tubular epithelial cells, the ATRAP protein colocalized with the AT(1) receptor. In renal biopsy specimens with IgA nephropathy, a significant positive correlation between ATRAP and AT(1) receptor gene expression was observed. There was also a positive relationship between tubulointerstitial ATRAP expression and the estimated glomerular filtration rate in patients with IgA nephropathy. Furthermore, we examined the function of the tubular AT(1) receptor using an immortalized cell line of mouse distal convoluted tubule cells (mDCT) and found that overexpression of ATRAP by adenoviral gene transfer suppressed the angiotensin II-mediated increases in transforming growth factor-β production in mDCT cells. These findings suggest that ATRAP might play a role in balancing the renal renin-angiotensin system synergistically with the AT(1) receptor by counterregulatory effects in IgA nephropathy and propose an antagonistic effect of tubular ATRAP on AT(1) receptor signaling.
authors.affiliation: Dept. of Medical Science and Cardiorenal Medicine, Yokohama City Univ. Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wakui
authors.forename: Akinobu
authors.initials: A
authors.lastname: Maeda
authors.forename: Toru
authors.initials: T
authors.lastname: Dejima
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirose
authors.forename: Masao
authors.initials: M
authors.lastname: Toyoda
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Masato
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kanaoka
authors.forename: Mai
authors.initials: M
authors.lastname: Yanagi
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsuhashi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Matsuda
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishigami
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Toya
authors.forename: Daisuke
authors.initials: D
authors.lastname: Suzuki
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001706:Biopsy; D002460:Cell Line; D003430:Cross-Sectional Studies; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008297:Male; D051379:Mice; D023421:Models, Animal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: C449676:AGTRAP protein, human; D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1