KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts.
The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-beta. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases.
Ohshimo
Shinichiro
S
Department of Molecular and Internal Medicine, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Yokoyama
Akihito
A
Hattori
Noboru
N
Ishikawa
Nobuhisa
N
Hirasawa
Yutaka
Y
Kohno
Nobuoki
N
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000097:blood / Q000502:physiology*; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006023:Glycoproteins / Q000097:blood / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000166:cytology*; D017563:Lung Diseases, Interstitial / Q000097:blood; D018396:Mucin-1; D009077:Mucins / Q000097:blood / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D000951:Antigens, Neoplasm; D016207:Cytokines; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins