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.
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Received: May 2, 2001 / Accepted: November 27, 2001
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Eto, Y., Shimosawa, T., Nitta, K. et al. Interaction between adrenomedullin and angiotensin II in DNA synthesis and extracellular matrix accumulation in cultured rat kidney interstitial cells. Clin Exp Nephrol 6, 7–12 (2002). https://doi.org/10.1007/s101570200001
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DOI: https://doi.org/10.1007/s101570200001