Interaction between adrenomedullin and angiotensin II in DNA synthesis and extracellular matrix accumulation in cultured rat kidney interstitial cells

2002 ◽  
Vol 6 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Y. Eto *, † , T. Shimosawa *, & ◽  
H. Nihei ◽  
N. Maruyama
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Dna Synthesis ◽  
Rat Kidney ◽  
Interstitial Cells ◽  
Matrix Accumulation

Angiotensin II Enhances Glomerular Expression of a Nonmuscle Myosin Heavy Chain, SMemb, with Extracellular Matrix Accumulation

Nephron ◽  
2002 ◽  
Vol 90 (4) ◽  
pp. 477-483 ◽  
Author(s):  
Naobumi Mise ◽  
Kenjiro Kimura ◽  
Masahiko Kurabayashi ◽  
Ryozo Nagai ◽  
Toshihiro Okuda ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Nonmuscle Myosin ◽  
Matrix Accumulation

Regulation of glomerular volume in normal and partially nephrectomized rats

1996 ◽  
Vol 270 (2) ◽  
pp. F356-F370 ◽  
Author(s):  
P. Cortes ◽  
X. Zhao ◽  
B. L. Riser ◽  
R. G. Narins
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Structural Changes ◽  
Mesangial Cells ◽  
Glomerular Volume ◽  
Matrix Accumulation ◽  
Relationship Of ◽  
The Relationship ◽  
Glomerular Extracellular Matrix ◽  
Intraglomerular Pressure

Glomerular extracellular matrix accumulation may derive from the stretching of mesangial cells caused by excessive glomerular dilatation. The relationship of glomerular volume (VG) to intraglomerular pressure, expressed as compliance or as mean VG in the isolated, perfused rat glomerulus, was used to analyze factors that regulate VG. Glomeruli were highly distensible over the normal and relevant abnormal range of pressure. Compliance increased directly with basal VG (P < 0.001), i.e., larger glomeruli dilated more than smaller ones at any given pressure. Perfusion with atrial natriuretic peptide did not alter compliance, and inhibitors of nitric oxide synthesis exerted only a trivial effect. VG expansion was consistently reduced by angiotensin II, but this effect was small (3.8%, P < 0.001). After subtotal nephrectomy, compliance increased by 59% in the remnant glomeruli (P < 0.001); 22% of this increase was attributable to structural changes, and the remainder was attributable to the large basal VG of the hypertrophied glomeruli. Thus the major determinants of VG expansion include capillary wall tension, basal VG, and intrinsic distensibility, which is markedly influenced by the character of the extracellular matrix and only slightly altered by an angiotensin II-modified mesangial cell tone.

Effects of angiotensin II on cultured rat renomedullary interstitial cells are mediated by AT1A receptors

1996 ◽  
Vol 271 (5) ◽  
pp. F1020-F1028 ◽  
Author(s):  
C. Maric ◽  
G. P. Aldred ◽  
A. M. Antoine ◽  
R. G. Dean ◽  
E. Eitle ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Interstitial Cells ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Vasoactive Peptides ◽  
Polymerase Chain ◽  
Second Messenger Pathways

Renomedullary interstitial cells (RMICs) are prominent in the inner medullary interstitium and have binding sites for several vasoactive agents, including angiotensin II (ANG II). Although the functional role of RMICs remains largely unknown, it is likely that the interaction between RMICs and vasoactive peptides is important in the regulation of renal function. The current investigation characterizes the cellular responses following treatment of RMICs with ANG II. Studies were performed on RMICs isolated from Sprague-Dawley rat kidneys. 125I-labeled [Sar1,Ile8]ANG II specifically bound to RMICs at sites determined by reverse transcription-polymerase chain reaction to be of the AT1A subtype. ANG II (10(-6) and 10(-10) M) had no effect on either basal or forskolin-stimulated adenosine 3',5'-cyclic monophosphate accumulation in RMICs but increased intracellular inositol 1,4,5-trisphosphate concentration after 10 s and intracellular calcium concentration after 18 s. For RMICs plated at low densities, ANG II (10(-6) M) induced an increase in [3H]thymidine incorporation, mediated through the AT1-receptor subtype. For RMICs plated at high densities, ANG II (10(-6) M) induced an increase in extracellular matrix synthesis as detected by trans-35S incorporation, an effect also mediated by AT1 receptors. We conclude that ANG II AT1A receptors on cultured RMICs are coupled to intracellular second messenger pathways leading to hyperplasia and synthesis of extracellular matrix.

scholarly journals β-Arrestin-biased AT1R stimulation promotes extracellular matrix synthesis in renal fibrosis

2017 ◽  
Vol 313 (1) ◽  
pp. F1-F8 ◽  
Author(s):  
Yandao Wang ◽  
Jieli Huang ◽  
Xi Liu ◽  
Yangyang Niu ◽  
Liqin Zhao ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
G Protein ◽  
Intracellular Signaling ◽  
Renal Fibrosis ◽  
Rat Kidney ◽  
Critical Role ◽  
Tight Binding ◽  
Renin Angiotensin System

The renin-angiotensin system plays a critical role in the progression of renal fibrosis. Angiotensin II type 1 receptor (AT1R) belongs to the B family of the G protein-coupled receptor (GPCR) family. β-Arrestins are known as negative regulators of GPCRs. Recently, β-arrestins have been found to regulate multiple intracellular signaling pathways independent of G proteins. In this study we investigated the role of β-arrestins in regulating extracellular matrix (ECM) synthesis in renal fibrosis. The rat kidney fibroblast cell line (NRK-49F) was treated with the β-arrestin biased agonist [1-sar, 4, 8-ile]angiotensin II (SII), which does not initiate AT1R-G protein signaling. The cells were transfected with recombinant adenoviruses expressing β-arrestin-2 gene or small-interfering RNA (siRNA) targeting β-arrestin-2. The unilateral ureteral obstruction (UUO) model was used in vivo. mRNA and protein levels of β-arrestin-2, not β-arrestin-1, were significantly upregulated in the UUO kidney tissues. SII induced the tight binding of β-arrestin-2 with AT1R. SII increased the synthesis of collagen I and fibronectin in NRK-49F, which were abolished when pretreated with candesartan (AT1R blocker). Transfection of siRNA targeting β-arrestin-2 decreased the effects of SII on ECM synthesis. Overexpression of β-arrestin-2 enhanced SII-stimulated ECM synthesis. SII induced ERK1/2 phosphorylation in NRK-49F. Transfection of siRNA targeting β-arrestin-2 inhibited ERK phosphorylation. Overexpression of β-arrestin-2 increased ERK1/2 phosphorylation. Our study first showed that AT1R-β-arrestin-2 pathway signaling plays an important role in renal fibrosis, although it was previously believed that the AT1R-G protein pathway plays a major role. Targeting β-arrestin-2 may be a potential therapeutic agent for renal fibrosis.

scholarly journals All-trans retinoic acid regulating angiopoietins-1 and alleviating extracellular matrix accumulation in interstitial fibrosis rats

Renal Failure ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 658-663
Author(s):  
Zhiqing Zhong ◽  
Hong-Yan Li ◽  
Hongzhen Zhong ◽  
Wenshan Lin ◽  
Shujun Lin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Retinoic Acid ◽  
Interstitial Fibrosis ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Matrix Accumulation

scholarly journals RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serina Yokoyama ◽  
Tatsuo Kawai ◽  
Koichi Yamamoto ◽  
Huang Yibin ◽  
Hiroko Yamamoto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Epithelial Cells ◽  
G Protein ◽  
Rat Kidney ◽  
Chinese Hamster ◽  
Cellular Responses ◽  
Type I ◽  
Α Subunit ◽  
Mesenchymal Transition

AbstractThe receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands. We generated Chinese hamster ovary (CHO) cells stably expressing RAGE and AT1, mutated AT1, or AT2 receptor. The activation of two types of G protein α-subunit, Gq and Gi, was estimated through the accumulation of inositol monophosphate and the inhibition of forskolin-induced cAMP production, respectively. Rat kidney epithelial cells were used to assess RAGE ligand-induced cellular responses. We determined that RAGE ligands activated Gi, but not Gq, only in cells expressing RAGE and wildtype AT1. The activation was inhibited by an AT1 blocker (ARB) as well as a RAGE inhibitor. ARBs inhibited RAGE ligand-induced ERK phosphorylation, NF-κB activation, and epithelial–mesenchymal transition of rat renal epithelial cells. Our findings suggest that the activation of AT1 plays a central role in RAGE-mediated cellular responses and elucidate the role of a novel molecular mechanism in the development of cardiovascular diseases.

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