Up-regulation of skeletal muscle LIM protein 1 gene by 25-hydroxycholesterol may mediate morphological changes of rat aortic smooth muscle cells.
Changes in the expression level of the skeletal muscle LIM protein 1 (SLIM1) in cultured A10 cells were monitored in response to 25-hydroxycholesterol (25-HC), an oxidized form of cholesterol present in the oxidized low-density lipoproteins. The level of SLIM1 mRNA was elevated in a time- and concentration-dependent manner by treatment of 25-HC. Expressions of smooth muscle (SM) alpha-actin and calponin-1 (CNN-1), early markers for SMC differentiation, were also increased by the 25-HC treatments. Expressions of all three genes (SLIM1, SM alpha-actin and CNN-1) were simultaneously elevated in the cells treated with 9-cis retinoic acid (RA). On the other hand, the SLIM1 expression induced by the 25-HC or 9-cis RA (as well as SM alpha-actin and CNN-1) was decreased by the treatment of 15d-PGJ2. Since the 25-HC, 9-cis RA and 15d-PGJ2 were ligands for the LXR, RXRalpha and PPARgamma respectively, there might be a functional positive cross-talk between LXR and RXRalpha pathways and a negative cross-talk between PPARgamma and LXR and/or RXRalpha pathways in the regulation of SLIM1 expression. The cells stably transfected with the expressional vector for SLIM1 also showed an elevation in the levels of SM alpha-actin and CNN-1. In addition, an over-production of SLIM1 in the cells resulted in a change in the cell-shape into a spindle-like form, which is identical to that observed after a prolonged treatment of the cells with cholesterol.
Kang
Mi Ae
MA
Department of Genetic Engineering, Kyungpook National University, 702-701, Republic of Korea.
Jeoung
Nam Ho
NH
Kim
Ji Young
JY
Lee
Ju Eui
JE
Jung
Un Ju
UJ
Choi
Myung-Sook
MS
Lee
Won-Ha
WH
Kwon
Oh-Shin
OS
Lee
Hyosun
H
Park
Yong Bok
YB
D000199:Actins / Q000235:genetics; D000077556:Alitretinoin; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D060588:LIM Domain Proteins; D008840:Microfilament Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation; D000096985:Calponins
D000199:Actins; D000077556:Alitretinoin; D002135:Calcium-Binding Proteins; D006888:Hydroxycholesterols; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D015230:Prostaglandin D2; D014212:Tretinoin; D000096985:Calponins; C477819:15-deoxyprostaglandin J2; C517184:Fhl1 protein, rat; C007997:25-hydroxycholesterol