Transforming growth factor beta induces vascular endothelial growth factor elaboration from pleural mesothelial cells in vivo and in vitro

Am J Respir Crit Care Med. 2002 Jan 1;165(1):88-94. doi: 10.1164/ajrccm.165.1.2104006.


Vascular endothelial growth factor (VEGF) increases vascular permeability and is important in pleural effusion formation. In studies using transforming growth factor beta (TGF-beta) to produce pleurodesis, we observed that although TGF-beta was more effective than talc or doxycycline, it induced transient production of large pleural effusions. We hypothesized that TGF-beta stimulates VEGF production in pleural tissues in vivo, and by mesothelial cells in vitro. New Zealand White rabbits (n = 33) were given TGF-beta(2) (1.7 or 5.0 microg), talc (400 mg/kg), doxycycline (10 mg/kg), or buffer intrapleurally. Pleural fluid was collected at 24 h. Intrapleural injection of TGF-beta(2) induced a dose-dependent increase in VEGF production. The pleural fluid VEGF level was 2-fold higher in rabbits given 5.0 microg of TGF-beta(2) than in those given 1.7 microg of TGF-beta(2) and 3-fold higher than in those given buffer. VEGF levels were higher after the injection of TGF-beta(2) than after administration of talc or doxycycline. The pleural fluid VEGF correlated significantly with the volume of pleural effusions (r = 0.79, p < 0.00001). In vitro, TGF-beta(2) stimulated a dose-dependent increase in VEGF production from murine pleural mesothelial cells. At 4 and 24 h, TGF-beta(2), but not talc or doxycycline, induced a significant increase in VEGF, when compared with controls. The mesothelial cell VEGF production was significantly reduced by anti-TGF-beta antibody in the TGF-beta(2), talc, and control (buffer and medium) groups. In conclusion, mesothelial cells are an important source of VEGF. TGF-beta increases the VEGF production by mesothelial cells in vivo and in vitro.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Capillary Permeability / drug effects*
  • Capillary Permeability / physiology*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Doxycycline / pharmacology
  • Doxycycline / therapeutic use
  • Drug Evaluation, Preclinical
  • Endothelial Growth Factors / physiology*
  • Epithelium / drug effects*
  • Epithelium / metabolism*
  • L-Lactate Dehydrogenase / analysis
  • Leukocyte Count
  • Linear Models
  • Lymphokines / drug effects*
  • Lymphokines / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Pleura / cytology*
  • Pleural Effusion / chemistry
  • Pleural Effusion / cytology
  • Pleural Effusion / drug therapy*
  • Pleural Effusion / etiology*
  • Pleurodesis / adverse effects*
  • Pleurodesis / methods*
  • Proteins / analysis
  • Rabbits
  • Talc / pharmacology
  • Talc / therapeutic use
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology*
  • Transforming Growth Factor beta / therapeutic use*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Proteins
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Talc
  • L-Lactate Dehydrogenase
  • Doxycycline