Hypoxia and transforming growth factor-beta 1 act independently to increase extracellular matrix production by placental fibroblasts.
Villous fibrosis is associated with oxygen deprivation in placental pathology, but the signaling networks and growth factors involved in activating the relevant cellular repair mechanisms are largely unknown. TGF is a powerful enhancer of extracellular matrix (ECM) production and an important immune suppressor that has been linked with fibrosis in several tissues. Here, cell culture methods were used to investigate possible links between hypoxia, elevated TGF beta 1, and altered ECM production in placenta. Term placental fibroblasts were isolated and cultured under hypoxia (3% O(2)) or in the presence of TGF beta 1, and the expression of fibronectin, collagen I, and collagen IV was examined using immunohistochemistry, ELISA of cell monolayers with associated ECM, and real-time RT-PCR. The effect of hypoxia on endogenous production of TGF beta 1-3 was also examined. Both TGF beta 1 and hypoxia increased fibronectin, collagen I, and collagen IV protein and mRNA in placental fibroblasts. However, TGF beta 1-3 production was not increased by culturing the cells under hypoxic conditions for 5 d. Thus, increased ECM expression under hypoxia was not mediated directly by increased TGF beta. We conclude that ECM production can be stimulated independently by hypoxia and TGF beta 1.
Chen
Chie-Pein
CP
Division of High Risk Pregnancy, Mackay Memorial Hospital, Taipei 104, Taiwan.
Yang
Yuh-Cheng
YC
Su
Tsung-Hsien
TH
Chen
Chia-Yu
CY
Aplin
John D
JD
D001483:Base Sequence; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D004261:DNA Replication; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D006801:Humans; D010920:Placenta / Q000166:cytology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D017931:DNA Primers; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1