Expression of FACIT collagens XII and XIV during bleomycin-induced pulmonary fibrosis in mice.
Collagens XII and XIV are members of a subfamily of fibril-associated collagens with interrupted triple-helices (FACITs) that facilitate the interactions of adjacent collagen fibrils. Using immunohistochemistry and in situ hybridization, we analyzed the spatial and temporal expression pattern of collagens XII and XIV during bleomycin-induced pulmonary fibrosis. C57Bl mice were treated with bleomycin (1 U, i.p., every other day for 8 days) or saline (control), and lung tissue samples were analyzed 2-12 weeks later. Collagen I protein expression was increased in the lung 2 weeks post bleomycin treatment and persisted for at least 12 weeks. In contrast, collagen XII and XIV expression was low until 4 weeks after bleomycin treatment. Whereas collagen XII expression was greatest between 4 weeks and 8 weeks, expression of collagen XIV persisted from 4 to 12 weeks, which suggests that these two proteins may play distinct roles in the fibrotic process. The mRNA for lysyl oxidase (LOX), an enzyme for cross-linking of collagens, had a delayed increase in the lung after bleomycin administration. It reached a maximum after 8 weeks, and persisted throughout the 12 weeks of the study. These data support the hypothesis that fibrosis is a multistep process that involves both collagen accumulation and changes in the molecules that modulate the biomechanical properties of fibrils.
Tzortzaki
Eleni G
EG
Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
Tischfield
Jay A
JA
Sahota
Amrik
A
Siafakas
Nikolaos M
NM
Gordon
Marion K
MK
Gerecke
Donald R
DR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D024082:Collagen Type XII / Q000378:metabolism*; D005260:Female; D024021:Fibril-Associated Collagens / Q000378:metabolism*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006023:Glycoproteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008249:Protein-Lysine 6-Oxidase / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; C054447:COL14A1 protein, human; C504563:Col14a1 protein, mouse; D024042:Collagen Type I; D024082:Collagen Type XII; D024021:Fibril-Associated Collagens; D006023:Glycoproteins; D012333:RNA, Messenger; D001761:Bleomycin; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase