Klotho is a recently discovered antiaging
protein. Although many researchers are investigating the roles of Klotho in
chronic kidney diseases and
cancer, however, there are no studies on the roles of Klotho in chronic
pulmonary diseases. The purpose of this study was to define the role of Klotho in
pulmonary fibrosis using a murine model of
ovalbumin (OVA)-induced chronic
asthma and in BEAS-2B human bronchial epithelial cells. In an in vivo experiment, mice were sensitized by
intraperitoneal injection of OVA (20 μg/mouse), followed 1 week later by an airway challenge with 1 % OVA
solution delivered three times a week for 4 weeks. In an in vitro experiment, we investigated the effects of stimulated with
interleukin (IL)-4 and
tumor necrosis factor (TNF)-α on Klotho
protein and
VEGF and
transforming growth factor (TGF)-β1/Smad3 signaling in BEAS-2B cells. Klotho decreased and
VEGF and TGF-β1 levels increased with increasing duration of OVA challenge. Similar findings were found for the expression of these
proteins in lung tissue. The
collagen content in lung tissue increased with repeated OVA challenge. In the in vitro experiment, Klotho expression decreased and
VEGF and TGF-β1/Smad3 expression increased after
IL-4 (50 ng/mL) and TNF-α (50 ng/mL) stimulation. Pretreatment with 25, 50, and 100 ng/mL of Klotho
protein significantly attenuated the increases in
VEGF and TGF-β1/Smad3 expression levels after
IL-4 and TNF-α treatment, and reduced α-smooth muscle actin expression in concentration-dependent manner. Klotho
protein inhibited the fibrotic response by suppressing
VEGF and TGF-β1/Smad3 expression. These results suggest that Klotho
protein may be crucial to inhibiting
fibrosis associated with chronic airway diseases.