Sp1 and Sp3 Transcription Factors Mediate Leptin-Induced Collagen α1(I) Gene Expression in Primary Culture of Male Rat Hepatic Stellate Cells

Mechanisms by which leptin stimulates collagen α1(I) [Col1a(I)] gene expression are unclear. The purposes of this study were to identify the trans-acting factors and cis-acting elements in Col1a(I) promoter involved in this effect as well as the pathways that are implicated. In primary cultures of rat hepatic stellate cells (HSCs), we measured the effects of leptin on Col1a(I) gene and protein expression and on the binding of nuclear proteins to the Col1a(I) promoter. We found that leptin increased Col1a(I) gene and protein expression in activated HSCs. Transient transfections showed that leptin exerted its effects through elements located between −220 and −112 bp of the Col1a(I) promoter. Gel retardation assays demonstrated that leptin induced the binding of transcription factors specific protein (Sp)-1 and Sp3 to two elements located between −161 and −110 bp of the Col1a(I) promoter. Leptin-induced Sp1/Sp3 phosphorylation, but this effect was suppressed by inhibiting or silencing Janus kinase-2, phospha...