The localization of adrenomedullin in rat kidney tissue and its inhibitory effect on the growth of cultured rat mesangial cells.
OBJECTIVE
To observe the localization of adrenomedullin (AM) in rat kidney tissue and its inhibitory effect on the growth of cultured rat mesangial cells (MsC).


METHODS
A monoclonal antibody against AM developed by our laboratory was used to detect the localization of AM protein in rat kidney tissue by avidin-biotin complex immunohistochemistry. The expressions of AM and its receptor CRLR mRNA on cultured glomerular epithelial cells (GEC) and MsC were investigated by Northern blot assay, and the possible effect of AM secreted by GEC on MsC proliferation was observed using [3H]thymidine incorporation as an index.


RESULTS
A specific monoclonal antibody against AM was succesfully developed. AM was immunohistochemically localized mainly in glomeruli (GEC and endothelial cells), some cortical proximal tubules, medullary collecting duct cells, interstitial cells, vascular smooth muscle cells and endothelial cells. Northern blot assay showed that AM mRNA was expressed only on cultured GEC, but not on MsC, however, AM receptor CRLR mRNA was only expressed on MsC. GEC conditioned medium containing AM can inhibit MsC growth and AM receptor blocker CGRP8-37 may partially decreased this inhibitory effect.


CONCLUSIONS
AM produced by GEC inhibits the proliferation of MsC, which suggests that AM as an important regulator is involved in glomerular normal physiological functions and pathologic processes.
Liu
Xueguang
X
Department of Pathology, School of Basic Medical Sciences, Medical Center, Fudan University, Shanghai 200032.
Zhang
Zhigang
Z
Zhang
Xiurong
X
Zhu
Hongguang
H
Chen
Qi
Q
Guo
Muyi
M
D053607:Adrenomedullin; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D058286:Calcitonin Receptor-Like Protein; D002455:Cell Division; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018003:Receptors, Calcitonin / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; C545580:Calcrl protein, rat; D010455:Peptides; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D053607:Adrenomedullin