| First Author | Jourdan-Le Saux C | Year | 1997 |
| Journal | J Cell Biochem | Volume | 64 |
| Issue | 2 | Pages | 328-41 |
| PubMed ID | 9027591 | Mgi Jnum | J:40413 |
| Mgi Id | MGI:87756 | Doi | 10.1002/(sici)1097-4644(199702)64:2<328::aid-jcb14>3.3.co;2-h |
| Citation | Jourdan-Le Saux C, et al. (1997) Functional analysis of the lysyl oxidase promoter in myofibroblast-like clones of 3T6 fibroblast. J Cell Biochem 64(2):328-41 |
| abstractText | Lysyl oxidase (LO), an extracellular enzyme catalysing the first step of collagen and elastin cross-linking, is transiently expressed by myofibroblasts during fibrosis. A cell model with features of myofibroblast was thus established for studying the regulation of LO. Two clones of the 3T6 fibroblast cell line were selected because 1) they produced a relatively high steady-state level of the three lysyl oxidase mRNAs with the same relative ratio similar to fibrotic tissue and 2) they stably displayed certain features of myofibroblast (alpha-smooth muscle actin cytoskeleton, bundles of cytoskeletal filaments beneath the cytoplasmic membranes). These clones synthesized predominantly type I collagen fibers and a small amount of type III collagen. Neither type IV collagen nor elastin were observed. The cloning and sequencing of 2,073 bp of the mouse Balb/C LO promoter was performed, allowing the identification around the initiation of transcription of consensus sequences which are found on the COL1 promoters. A series of deletion constructs containing the LO 5'-flanking region ligated to the luciferase gene were transiently transfected into 3T6-5 fibroblasts. The region allowing the maximal activity was found between positions -416 to -192, while the more upstream region negatively regulated the promoter. The -898 to -865 sequence (called LOcol1) displayed 79% of homology with a conserved sequence of murine, rat, and human COL1A1 promoters. This sequence participated to the binding of several nuclear factors within a region (-970 to -784) allowing 50% of inhibition of the LO promoter. Therefore, the level of LO transcription is regulated in 3T6-5 fibroblast by positive and negative cis-acting regulatory elements which might have common features with the COL1A1 promoter. |
