Administration of keratinocyte growth factor down-regulates the pulmonary capacity of acetylcholine production.
Keratinocyte growth factor protects the lung against various injurious stimuli. The protective mechanisms, however, are not yet fully understood. The aim of this study is to determine the influence of keratinocyte growth factor on the pulmonary capacity to synthesize acetylcholine, a potent regulator of pulmonary functions which is potentially involved in lung damage. Rats were treated twice (days 1 and 2) intratracheally with keratinocyte growth factor and analyzed at day 4. The mRNA expression of choline acetyltransferase - the acetylcholine synthesizing enzyme - was analyzed by real-time RT-PCR in the lung and in isolated alveolar epithelial type II cells. Choline acetyltransferase protein was assessed by immunoblotting and immunohistochemistry. Finally, pulmonary acetylcholine content was assessed biochemically. Keratinocyte growth factor-treatment led to decreased levels of choline acetyltransferase mRNA in the lung and in isolated alveolar epithelial type II cells. Accordingly, pulmonary choline acetyltransferase protein levels were reduced and pulmonary acetylcholine content declined from 2.8 nmol (control) to 0.4 nmol acetylcholine per gram of wet weight. In conclusion, the present data show that the potent regulator of pulmonary functions, acetylcholine, is produced by the major pulmonary target cell of keratinocyte growth factor, that is alveolar epithelial type II cells. Acetylcholine synthesis is down-regulated by keratinocyte growth factor administration which might contribute to lung protection and to harmonize surfactant homeostasis under conditions of keratinocyte growth factor-induced alveolar epithelial type II cell hyperplasia.
Grau
Veronika
V
Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, University of Giessen Lung Center, Justus-Liebig-University Giessen, Rudolf Buchheim Str. 7, D-35385 Giessen, Germany. Veronika.Grau@chiru.med.uni-giessen.de
Wilker
Sigrid
S
Lips
Katrin S
KS
Hartmann
Petra
P
Rose
Frank
F
Padberg
Winfried
W
Fehrenbach
Heinz
H
Wessler
Ignatz
I
Kummer
Wolfgang
W
D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology
C501512:CHT1 protein, rat; D027682:Cation Transport Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine