Journal of Applied Physiology AJP: Endocrinology and Metabolism
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J Appl Physiol (October 17, 2003). doi:10.1152/japplphysiol.00783.2003
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Submitted on July 25, 2003
Accepted on October 9, 2003

Keratinocyte growth factor transiently alters pulmonary function in rats

Jens M Hohlfeld1*, Heinz G Hoymann2, Thomas Tschernig3, Antonia Fehrenbach4, Norbert Krug2, and Heinz Fehrenbach4

1 Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; Department of Immunology, Allergology and Clinical Inhalation, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
2 Department of Immunology, Allergology and Clinical Inhalation, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
3 Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany
4 Clinical Research Group Chronic Airway Diseases, University Marburg, Marburg, Germany

* To whom correspondence should be addressed. E-mail: hohlfeld.jens{at}mh-hannover.de.

Keratinocyte growth factor (KGF) is a mitogen for pulmonary epithelial cells. Intratracheal administration of KGF to adult rats results in alveolar epithelial type II and bronchiolar epithelial cell proliferation. While cellular responses to KGF have been intensively studied, functional consequences regarding lung function are unknown. Therefore, in this study we sought to investigate whether KGF alters pulmonary function variables. Rats received either recombinant human KGF (rHuKGF) (5 mg/kg) or vehicle intratracheally. Prior to and on days 3 and 7 after treatment, pulmonary function was determined by body plethysmography. Subsequently, lung histological changes were quantified. rHuKGF induced a transient proliferation of alveolar and bronchiolar epithelial cells. The extend of type II cell hyperplasia was significantly correlated with a transient reduction of tidal volume and an increase in breathing frequency. In addition, quasistatic compliance, total lung capacity and vital capacity were reduced following rHuKGF instillation suggesting the development of a transitory restrictive lung disorder. Moreover, reduced expiratory flow rates and forced expiratory volumes as well as increased functional residual capacity after rHuKGF but not vehicle suggest obstructive lung function changes. In conclusion, the induction of alveolar and bronchiolar epithelial cell proliferation by KGF is paralleled by moderate functional consequences that should be taken into account when the therapeutic potential of KGF is tested.




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