Tags

Type your tag names separated by a space and hit enter

Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells.
Biochem Biophys Res Commun. 2004 Apr 09; 316(3):712-9.BB

Abstract

Smad6 and Smad7 are inhibitory Smads (I-Smads) with differential inhibitory effects on the regulation of the cellular signalings induced by TGF-beta superfamily. Here, we show that phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) down-regulates Smad6 mRNA expression and up-regulates Smad7 mRNA expression in IMR-90, a human lung fibroblast cell line. These regulations of I-Smads by TPA were suppressed by one PKC inhibitor (Gö6983), but not by another (Gö6976). TPA treatment had little effect on the phosphorylation of novel PKCs (PKCdelta and PKCepsilon), but specifically induced PKCmu phosphorylation, and this effect was inhibited by Gö6983, but not by Gö6976. Additionally, Gö6983 but not Gö6976 inhibited ERK- and JNK-phosphorylation as well as Smad7 promoter activity induced by TPA. MEK inhibitor U0126 inhibited the down-regulation of Smad6 mRNA expression but not the up-regulation of Smad7 mRNA expression. In contrast, JNK inhibitor SP600125 had no such effects. Luciferase reporter analysis revealed that TPA did not induce NF-kappaB activation. In addition, TPA up-regulated Smad7 expression in the presence of NF-kappaB inhibitor TLCK. These findings indicate that TPA down-regulates Smad6 expression presumably via PKCmu-ERK-dependent pathway and up-regulates Smad7 expression via PKCmu-dependent mechanism(s) which need no MAPK and NF-kappaB activation.

Authors+Show Affiliations

Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan. h-tsunobuchi@aist.go.jpNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15033458

Citation

Tsunobuchi, Hironaka, et al. "Expressions of Inhibitory Smads, Smad6 and Smad7, Are Differentially Regulated By TPA in Human Lung Fibroblast Cells." Biochemical and Biophysical Research Communications, vol. 316, no. 3, 2004, pp. 712-9.
Tsunobuchi H, Ishisaki A, Imamura T. Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells. Biochem Biophys Res Commun. 2004;316(3):712-9.
Tsunobuchi, H., Ishisaki, A., & Imamura, T. (2004). Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells. Biochemical and Biophysical Research Communications, 316(3), 712-9.
Tsunobuchi H, Ishisaki A, Imamura T. Expressions of Inhibitory Smads, Smad6 and Smad7, Are Differentially Regulated By TPA in Human Lung Fibroblast Cells. Biochem Biophys Res Commun. 2004 Apr 9;316(3):712-9. PubMed PMID: 15033458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expressions of inhibitory Smads, Smad6 and Smad7, are differentially regulated by TPA in human lung fibroblast cells. AU - Tsunobuchi,Hironaka, AU - Ishisaki,Akira, AU - Imamura,Toru, PY - 2003/11/17/received PY - 2004/3/23/pubmed PY - 2004/5/21/medline PY - 2004/3/23/entrez SP - 712 EP - 9 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 316 IS - 3 N2 - Smad6 and Smad7 are inhibitory Smads (I-Smads) with differential inhibitory effects on the regulation of the cellular signalings induced by TGF-beta superfamily. Here, we show that phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) down-regulates Smad6 mRNA expression and up-regulates Smad7 mRNA expression in IMR-90, a human lung fibroblast cell line. These regulations of I-Smads by TPA were suppressed by one PKC inhibitor (Gö6983), but not by another (Gö6976). TPA treatment had little effect on the phosphorylation of novel PKCs (PKCdelta and PKCepsilon), but specifically induced PKCmu phosphorylation, and this effect was inhibited by Gö6983, but not by Gö6976. Additionally, Gö6983 but not Gö6976 inhibited ERK- and JNK-phosphorylation as well as Smad7 promoter activity induced by TPA. MEK inhibitor U0126 inhibited the down-regulation of Smad6 mRNA expression but not the up-regulation of Smad7 mRNA expression. In contrast, JNK inhibitor SP600125 had no such effects. Luciferase reporter analysis revealed that TPA did not induce NF-kappaB activation. In addition, TPA up-regulated Smad7 expression in the presence of NF-kappaB inhibitor TLCK. These findings indicate that TPA down-regulates Smad6 expression presumably via PKCmu-ERK-dependent pathway and up-regulates Smad7 expression via PKCmu-dependent mechanism(s) which need no MAPK and NF-kappaB activation. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/15033458/Expressions_of_inhibitory_Smads_Smad6_and_Smad7_are_differentially_regulated_by_TPA_in_human_lung_fibroblast_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006291X04003729 DB - PRIME DP - Unbound Medicine ER -