Inhibitory effects of polymyxin B on NF-kappaB activation and expression of procollagen I, III in pre-eclamptic umbilical artery smooth muscle cells.

Full Abstract

BACKGROUND: It has been identified that in patients with pre-eclampsia, several factors were released into the serum, which can regulate the proliferation of vascular smooth muscle cells and stimulate the synthesis of extracellular matrix (ECM). However, the signal transduction pathway of the growth factors and cytokines synthesized by endothelial cells leading to the proliferation and ECM synthesis of human umbilical arterial smooth muscle cell (HUASMC) is unknown. The aim of this study was to research the effects of protein kinase C (PKC) inhibitor, polymyxin B (PMB), on the proliferation, nuclear factor-kappa B (NF-kappaB) activation, and expression of procollagen I and III mRNA in HUASMC cultured with pre-eclamptic umbilical sera. METHODS: Normal HUASMCs were treated with pre-eclamptic umbilical serum (pre-eclamptic group), pre- eclamptic umbilical serum plus PMB (PMB group), or normal umbilical serum (normal group). The expression of I-kappaB, NF-kappaB was detected by Western blotting after the HUASMC was incubated for 2 hours. The proliferation of HUASMC was evaluated by MTT, the cell cycle was analyzed by flow cytomerty, and the expression of procollagen I, III mRNA was measured by RT-PCR assay after HUASMC was incubated for 48 hours. ANOVA was used for statistical analysis. RESULTS: Umbilical sera in pre-eclampsia could stimulate the proliferation, the DNA synthesis, the transition of G(0) + G(1) phase or G(2)/M phase to S and phase, the activation of NF-kappaB, and the expression of procollagen I mRNA of HUASMC as compared with normal umbilical sera (P < 0.01). PMB could inhibit the proliferation, the DNA synthesis, the transition of G(0) + G(1) or G(2)/M phase phase to S phase, the activation of NF-kappaB, and the expressions of procollagen I mRNA of HUASMC stimulated by umbilical sera in pre-eclampsia (P < 0.01). CONCLUSION: PKC-NF-kappaB signal transduction pathway may play a key role in SMC phenotype modulation, which is more important in the pathogenesis of placental blood vessel in pre-eclampsia.

Author information

Author/s: Jiang, Rong-zhen (RZ); Chen, Han-ping (HP); Xu, Xiao-yan (XY);

Affiliation: Department of Obstetrics and Gynecology, Shanghai Jiaotong University-Affiliated Sixth People's Hospital, Shanghai 200233, China. jianrzh(-atsign-)163.com

Journal and publication information

Publication Type: Journal Article

Journal: Chinese medical journal (Chin Med J (Engl)), published in China. (Language: eng)

Reference: 2006-Mar; vol 119 (issue 5) : pp 384-90

Dates: Created 2006/03/17; Completed 2006/04/06; Revised 2007/11/15;

PMID: 16542581, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cell Cycle - drug effects
Cell Proliferation - drug effects
Cells, Cultured
Collagen Type I - genetics
Collagen Type III - genetics
Female
Humans
Muscle, Smooth, Vascular - cytology; metabolism
Myocytes, Smooth Muscle - metabolism

Myocytes, Smooth Muscle - metabolism
NF-kappa B - physiology
Polymyxin B - pharmacology
Pre-Eclampsia - metabolism; pathology
Pregnancy
Protein Kinase C - antagonists & inhibitors; physiology
RNA, Messenger - analysis
Signal Transduction
Umbilical Arteries - metabolism

Associated Chemicals: Collagen Type I (0) ; Collagen Type III (0) ; NF-kappa B (0) ; RNA, Messenger (0) ; Polymyxin B (1404-26-8) ; Protein Kinase C (EC 2.7.11.13)

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