Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway.

Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway.
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肾上腺髓质素通过 cAMP 途径抑制大鼠系膜细胞的有丝分裂。

DOI:
10.1006/bbrc.1995.2544
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发表时间:
1995
期刊:
Biochemical and biophysical research communications.
影响因子:
--
通讯作者:
Dousa,TP
Dousa,TP
中科院分区:
--
文献类型:
--
作者:
Chini,EN;Choi,E;Grande,JP;Burnett,JC;Dousa,TP

文献摘要

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肾上腺髓质素(ADM)是近年发现的一种分布于肾小球的血管活性肽。本研究探讨ADM是否能刺激肾小球系膜细胞(MC)cAMP系统,并通过“负性串扰”抑制丝裂原活化蛋白激酶(MAPK),从而抑制MC增殖。我们发现,ADM引起的cAMP的积累和原位激活的蛋白激酶A(PKA)在培养的MC。加入1 nM ADM可抑制静止MC和PDGF最大刺激细胞的增殖,并降低PDGF诱导的MAPK活化。这些结果表明,ADM可以抑制MC有丝分裂,并建议它可能作为一个内源性旁分泌抑制MC增殖。
Adrenomedullin (ADM) is a vasoactive peptide that was recently localized in renal glomeruli. In the present study we explored whether ADM stimulates cAMP system in glomerular mesangial cells (MC) and whether it can via "negative-crosstalk" inhibit the mitogen-activated protein kinase (MAPK) and thus suppress proliferation of MC. We found that ADM elicited accumulation of cAMP and in situ activation of protein kinase A (PKA) in cultured MC. Addition of 1 nM ADM to incubation media inhibited the proliferation in both quiescent MC and cells maximally stimulated by PDGF and also decreased the activation of MAPK induced by PDGF. These results indicate that ADM can suppress MC mitogenesis and suggest that it may function as an endogenous paracrine supressor of MC proliferation.