Interaction between adrenomedullin and angiotensin II in DNA synthesis and extracellular matrix accumulation in cultured rat kidney interstitial cells |
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Authors: | Y Eto T Shimosawa K Nitta H Nihei N Maruyama |
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Institution: | (1) Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan, JP;(2) Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan, JP;(3) Department of Clinical Laboratory Medicine, The University of Tokyo, School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel. +81-3-3815-5411, ext 35007; Fax +81-3-5689-0495 e-mail: tshimo-tky@umin.ac.jp, JP |
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Abstract: | Background. To investigate the role of adrenomedullin (AM) in the regulation of renal fibrosis, we assessed the effects of AM on angiotensin
II (AT II)-induced cell proliferation and extracellular matrix (ECM) accumulation in cultured NRK 49F cells, a cell line derived
from normal rat kidney fibroblasts.
Methods. Northern blot analysis was performed, using cDNA probes against rat AM, human calcitonin-receptor-like receptor (CRLR), human
receptor-activity-modifying protein 2 (RAMP 2), human collagen α-1 (I) (Col-I), human fibronectin (FN), and rat transforming
growth factor (TGF)-β1. Polymerase chain reaction (PCR) analysis for CRLR was amplified for 35 cycles. Cell proliferation
was determined by the measurement of 3H]thymidine incorporation.
Results. We have shown that NRK 49F cells express AM and its receptor, which consists of a CRLR and RAMP 2. Rat AM significantly inhibited
cell proliferation and mRNA expression of ECM in the absence and presence of AT II through an AM receptor, because calcitonin
gene-related peptide (8-37) CGRP (8-37)], an antagonist to AM receptor, completely reversed these inhibitory actions. The
inhibitory effects appeared to be mediated by a marked increase in intracellular cAMP. While AT II enhanced ECM accumulation
by a process depending upon autocrine TGF-β1 secretion in NRK 49F cells, AM suppressed the induction of TGF-β1.
Conclusions. The inhibitory action of AM on ECM accumulation may be caused by the suppression of TGF-β1. AM may play an important role
in the inhibition of renal interstitial fibrosis under pathological conditions, through acting in an autocrine and/or paracrine
fashion.
Received: May 2, 2001 / Accepted: November 27, 2001 |
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Keywords: | Adrenomedullin Renal interstitial fibrosis RAMP 2 Angiotensin II |
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