Hsc70 facilitates TGF-β-induced activation of Smad2/3 in fibroblastic NRK-49F cells.
Heat-shock cognate protein 70 (Hsc70), a molecular chaperone constitutively expressed in the cell, is involved in the regulation of several cellular signaling pathways. In this study, we found that TGF-β-induced phosphorylation and nuclear translocation of Smad2/3 were suppressed in fibroblastic NRK-49F cells treated with small interfering RNA (siRNA) for Hsc70. In the cells underexpressing Hsc70, transcriptional induction of connective tissue growth factor (CTGF), a target gene of the TGF-β signaling, was also suppressed in the early phase of TGF-β stimulation. Upon stimulation with TGF-β, Hsc70 interacted with Smad2/3, suggesting functional interactions of Hsc70 and Smad2/3 for the activation of TGF-β-induced Smad signaling. Although the expression of heat-shock protein 70 (Hsp70) was upregulated in the cells treated with Hsc70 siRNA, TGF-β-induced Smad activation was not affected in the cells overexpressing Hsp70. Collectively, these results indicate that Hsc70, but not Hsp70, supportively regulates TGF-β-induced Smad signaling in NRK-49F cells.
Department of Biochemistry, Wakayama Medical University, Wakayama, Japan.
Midori
M
Ikezaki
Department of Biochemistry, Wakayama Medical University, Wakayama, Japan.
Natsuki
N
Higashimoto
Department of Biochemistry, Wakayama Medical University, Wakayama, Japan.
Ko
K
Matsumura
Department of Biochemistry, Wakayama Medical University, Wakayama, Japan. Electronic address: y-ihara@wakayama-med.ac.jp.
Yoshito
Y
Ihara
D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D050883:HSC70 Heat-Shock Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta
Hsc70; Hsp70; Smad2/3; TGF-β