Transcriptional repression of type I procollagen genes during adipocyte differentiation

Abstract

Adipocyte differentiation is a very complex process in which whole-cell changes are accompanied. Among them, type I procollagen gene has been shown to specifically decrease during adipocyte differentiation; however, little is known about the molecular mechanism. To examine how type I procollagen gene expression is regulated at the level of transcription during adipocyte differentiation, 3T3-L1 preadipocyte cell line was used as an in vitro model. Northern blot analysis demonstrated that mRNA expression of type I procollagen gene was dramatically reduced during adipocyte differentiation. Time-course analysis indicated that decrease in mRNA expression occurred at early stage of differentiation. Studies on several stable cell lines showed that transcriptional activities of both α1 and α2 promoters decreased significantly during adipocyte differentiation. Despite extensive deletion-promoter analyses, however, we could not identify the cis-element responsible for the switch-off of type I procollagen gene during adipocyte differentiation, suggesting that the transcriptional repression of this gene occur through general transcription machinery rather than a specific cis-element. In conclusion, down-regulation of type I procollagen mRNA expression during adipocyte differentiation is due to repression of its promoter activity through general transcription machinery.

Plasminogen activator inhibitor-1 modulates adipocyte differentiation

“…The plasminogen cascade has been postulated to foster adipocyte differentiation by degradation of the fibronectin-rich preadipocyte stromal matrix (56). In the present study, our observations of decreased expression of collagen I and increased expression of uPA after 3T3-L1 adipocyte differentiation are consistent with previous data (55,66). Interestingly, the inhibited adipocyte differentiation in PAI-1-overexpressing 3T3-L1 cells was associated with upregulated collagen I and downregulated uPA and plasmin.…”

“…It has been suggested recently that various factors in cell-cell and cellmatrix communications govern expression of adipocyte transcription factors and therefore regulate conversion of preadipocytes to adipocytes. During differentiation, expression of ECM components, including collagens and proteases, is changed (64,66). Indeed, adipocytes produce and release a variety of proteolytic proteins (9,11).…”

Subcutaneous fat in normal and diseased states

“…26,171,172 Emerging evidence suggests that ECM components play an important role in the regulation of adipose tissue remodeling during adipocyte differentiation and are necessary for progression of the adipogenic program. [172][173][174] The ECM not only influences the integrity of the structural system that supports cells, but also influences, via cell-surface receptors, cell-cell and cell-matrix interactions with impact on differentiation and cell migration. Modulation of ECM components during adipogenesis mediates cytoskeletal rearrangement, release of cell adhesion, and alteration of cell components necessary for changes in cell morphology.…”

“…Modulation of ECM components during adipogenesis mediates cytoskeletal rearrangement, release of cell adhesion, and alteration of cell components necessary for changes in cell morphology. 173 ECM changes not only influence the architectural and structural complexity of adipocytes, but also play an important role in transducing cellular signals with impact on adipocyte gene transcription during adipogenesis. Fibronectin, for example, an important cytoskeletal component of the ECM during initial stages of adipogenesis, inhibits adipogenesis at later stages, in part, by down-regulating the expression of lipogenic genes.…”

“…2,175,177,178 Collagen, the most abundant component of ECM, serves as a substratum for cell adhesion, migration, spreading, and anchorage-dependent growth. 173,175 As such, active synthesis of collagens during the preadipose state is required for preadipocyte differentiation. 174 During adipogenesis, a switch in collagen gene expression and secretion is noted.…”