Keratinocyte growth factor increases transalveolar sodium reabsorption in normal and injured rat lungs

Am J Respir Crit Care Med. 1997 May;155(5):1777-84. doi: 10.1164/ajrccm.155.5.9154891.


Keratinocyte growth factor (KGF) prevents alpha-naphthylthiourea (ANTU)-induced permeability edema ex vivo. To explore the mechanisms in this involved effect, we administered KGF (5 mg/kg, intratracheally) 48 h prior to ANTU (50 mg/kg, intraperitoneally). Several groups were studied: phosphate-buffered saline/dimethylsulfoxide (PBS/DMSO) (vehicles), PBS/ANTU, and KGF/ANTU. At 90 min after ANTU injection the lungs were removed, ventilated, and perfused ex vivo for 180 min. Quantification of fluorescein isothiocyanate (FITC)-labeled dextran in bronchoalveolar lavage fluid (BALF) was used to assess alveolar capillary barrier permeability. KGF attenuated ANTU-induced edema and blockade of sodium transport, with ouabain (10(-3) M) or amiloride (10(-4) M) added ex vivo reversed this effect. FITC-dextran was increased in the PBS/ANTU group as compared with the PBS/DMSO group, indicating permeability edema. In the KGF/ANTU group, there was concentration of BALF FITC-dextran, consistent with permeability edema and increased alveolar fluid export. Albumin space measurements showed similar increases in permeability in the PBS/ANTU and KGF/ANTU groups. Extravascular lung water (measured with radiolabeled erythrocytes) was decreased in the KGF/ANTU group. Following KGF pretreatment, uninjured lungs exported more intratracheal PBS than normal lungs following terbutaline stimulation ex vivo. In conclusion, KGF, through type II alveolar pneumocyte hyperplasia with increased sodium-potassium-adenosine triphosphatase (Na,K-ATPase) activity, attenuated ANTU-induced edema formation by potentiating alveolar fluid clearance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorption
  • Amiloride / pharmacology
  • Animals
  • Biological Transport
  • Bronchoalveolar Lavage Fluid / chemistry
  • Capillary Permeability
  • Dimethyl Sulfoxide / pharmacology
  • Enzyme Activation
  • Extravascular Lung Water / metabolism
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors*
  • Growth Substances / pharmacology*
  • Ouabain / pharmacology
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Alveoli / pathology
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / metabolism*
  • Pulmonary Edema / pathology
  • Pulmonary Edema / physiopathology
  • Rats
  • Sodium / metabolism*
  • Sodium Chloride
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Thiourea / analogs & derivatives


  • Fgf7 protein, rat
  • Fibroblast Growth Factor 10
  • Growth Substances
  • Fibroblast Growth Factor 7
  • Sodium Chloride
  • Ouabain
  • Fibroblast Growth Factors
  • Amiloride
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
  • Thiourea
  • alpha-naphthyl thiourea
  • Dimethyl Sulfoxide