title: Species differences in expression pattern of arginase isoenzymes and differential effects of arginase inhibition on collagen synthesis in human and rat pulmonary fibroblasts.
abstract: Arginase was shown to be up-regulated in different animal models of inflammatory and fibrotic airway diseases. Since arginase provides L-ornithine, one precursor for L-proline, an essential substrate for collagen synthesis, it has been suggested that arginase might be a key enzyme in airway remodelling. The present study aimed to characterize expression of arginase isoenzymes in rat and human pulmonary fibroblasts, and to test whether arginase inhibition affects collagen synthesis. In primary rat tracheal and lung fibroblasts, mRNA for arginase I and II could be detected, with arginase I as predominant isoenzyme. In contrast, in human lung fibroblasts (primary cells and different cells lines) mRNA levels for arginase I were at or below detection limit whereas arginase II mRNA was markedly higher than in rat pulmonary fibroblasts. Arginase activity in rat tracheal and lung fibroblasts was between 20 and 30 mU/mg protein, but was below detection limit (2.5 mU/mg) in human lung fibroblasts. In rat tracheal and lung fibroblasts cultured in proline-free medium, arginase inhibition by N(omega)-hydroxy-nor-L-arginine caused a reduction by about one-third of basal collagen I accumulation (determined by western blot analysis) and largely attenuated transforming growth factor beta 1 (TGF-beta(1))-induced increase in collagen accumulation, whereas basal and TGF-beta(1)-induced collagen accumulation by human lung fibroblasts was not affected by arginase inhibition. In conclusion, arginase isoenzymes reveal a species specific expression pattern. Arginase contributes significantly to L-proline supply for collagen synthesis in rat fibroblasts, in which arginase I is the predominant isoenzyme, but not in human fibroblasts, in which arginase II is the only isoenzyme expressed.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Bonn, Biomedical Center 2G028, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Warnken
authors.forename: S
authors.initials: S
authors.lastname: Haag
authors.forename: S
authors.initials: S
authors.lastname: Matthiesen
authors.forename: U R
authors.initials: UR
authors.lastname: Juergens
authors.forename: K
authors.initials: K
authors.lastname: Racké
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes; D008168:Lung / Q000166:cytology / Q000201:enzymology; D008297:Male; D011392:Proline / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014132:Trachea / Q000166:cytology / Q000201:enzymology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C068309:N(omega)-hydroxyarginine; D003094:Collagen; D001120:Arginine; D011392:Proline; C477631:ARG2 protein, human; C113162:Arg2 protein, rat; D001119:Arginase; C542908:arginase I, rat