cDNA cloning and chromosomal mapping of rat Smad2 and Smad4 and their expression in cultured rat articular chondrocytes

被引:9
作者
Osaki, M
Tsukazaki, T
Ono, N
Yonekura, A
Hirota, Y
Miyazaki, Y
Shindo, H
Sonta, S
Yamashita, S
机构
[1] Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Dept Nat Med, Nagasaki 8528523, Japan
[2] Nagasaki Univ, Sch Med, Dept Orthopaed Surg, Nagasaki, Japan
[3] Aichi Human Serv Ctr, Inst Dev Res, Dept Genet, Aichi, Japan
关键词
Smad2; Smad4; rat; mapping; chondrocyte;
D O I
10.1507/endocrj.46.695
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Smad proteins are known to transduce signalling of TGF-beta receptor superfamily. We report here the entire sequences of rat Smad2 and Smad4 which have not been identified yet. Entire sequences were identified by degenerated polymerase chain reaction and following phage library screening and 5' RACE. The predicted amino acid sequences of rat Smad2 and Smad4 are highly conserved among rat, human and mouse. We also mapped these Smads to chromosome 18q.12.3. Unlike endothelial cells, TGF-beta 1 stimulates articular chondrocyte proliferation as well as extracellular matrix production, and acts as a repairing agent against cartilage destruction. Since both Smad2 and Smad4 are essential factors for TGF-beta signalling, we examined their expression and regulation in cultured articular chondrocytes. Northern blot analysis showed that TGF-beta 1 significantly increased the mRNA level of Smad2 but not of Smad4 in a dose- and time-dependent manner, suggesting that the augmentation of TGF-beta 1 action is caused by increasing the expression of the downstream signalling molecule.
引用
收藏
页码:695 / 701
页数:7
相关论文
共 23 条
[1]   Mads and Smads in TGFβ signalling [J].
Attisano, L ;
Wrana, JL .
CURRENT OPINION IN CELL BIOLOGY, 1998, 10 (02) :188-194
[2]  
Attisano Liliana, 1996, Cytokine and Growth Factor Reviews, V7, P327, DOI 10.1016/S1359-6101(96)00042-1
[3]   TGF-BETA INDUCES BIMODAL PROLIFERATION OF CONNECTIVE-TISSUE CELLS VIA COMPLEX CONTROL OF AN AUTOCRINE PDGF LOOP [J].
BATTEGAY, EJ ;
RAINES, EW ;
SEIFERT, RA ;
BOWENPOPE, DF ;
ROSS, R .
CELL, 1990, 63 (03) :515-524
[4]   MODULATION OF RABBIT ARTICULAR CHONDROCYTE (RAC) PROLIFERATION BY TGF-BETA ISOFORMS [J].
BOUMEDIENE, K ;
VIVIEN, D ;
MACRO, M ;
BOGDANOWICZ, P ;
LEBRUN, E ;
PUJOL, JP .
CELL PROLIFERATION, 1995, 28 (04) :221-234
[5]   Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4 [J].
Hata, A ;
Lo, RS ;
Wotton, D ;
Lagna, G ;
Massague, J .
NATURE, 1997, 388 (6637) :82-87
[6]   INDUCTION OF C-SIS MESSENGER-RNA AND ACTIVITY SIMILAR TO PLATELET-DERIVED GROWTH-FACTOR BY TRANSFORMING GROWTH-FACTOR-BETA - A PROPOSED MODEL FOR INDIRECT MITOGENESIS INVOLVING AUTOCRINE ACTIVITY [J].
LEOF, EB ;
PROPER, JA ;
GOUSTIN, AS ;
SHIPLEY, GD ;
DICORLETO, PE ;
MOSES, HL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (08) :2453-2457
[7]   THE EL2 RAT FIBROBLASTS LINE - DIFFERENTIAL-EFFECTS OF GROWTH-FACTORS (EGF, PDGF, FGF, TPA AND TGF-BETA) ON CELL-PROLIFERATION AND C-FOS EXPRESSION [J].
LIBOI, E ;
PELOSI, E ;
DIFRANCESCO, P ;
GALLINARI, P ;
PETRINI, M ;
SPOSI, NM ;
TESTA, U ;
ROSSI, GB ;
PESCHLE, C .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1987, 511 :318-328
[8]   C-FOS PROTOONCOGENE IS INVOLVED IN THE MITOGENIC EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA IN OSTEOBLASTIC CELLS [J].
MACHWATE, M ;
JULLIENNE, A ;
MOUKHTAR, M ;
LOMRI, A ;
MARIE, PJ .
MOLECULAR ENDOCRINOLOGY, 1995, 9 (02) :187-198
[9]   MADR2 is a substrate of the TGF beta receptor and its phosphorylation is required for nuclear accumulation and signaling [J].
MaciasSilva, M ;
Abdollah, S ;
Hoodless, PA ;
Pirone, R ;
Attisano, L ;
Wrana, JL .
CELL, 1996, 87 (07) :1215-1224
[10]   TRANSFORMING GROWTH FACTOR-BETA-1 STIMULATES SYNTHESIS OF PROTEOGLYCAN AGGREGATES IN CALF ARTICULAR-CARTILAGE ORGAN-CULTURES [J].
MORALES, TI .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1991, 286 (01) :99-106