Regulation of Fgf10 Gene Expression in the Prostate: Identification of Transforming Growth Factor-β1 and Promoter Elements

Abstract

Fibroblast growth factor 10 (FGF10) is a mesenchymal paracrine-acting factor that plays a key role in the organogenesis of the prostate, and Fgf10 transcripts exhibit a highly restricted expression pattern within prostatic mesenchyme. To study the regulation of Fgf10 we have used organ rudiments grown in vitro as well as a primary stromal cell system derived from the ventral mesenchymal pad (VMP), a condensed area of mesenchyme known to induce prostatic organogenesis. Characterization of VMP cells (VMPCs) showed that they retained expression of AR as well as transcripts for FGF10 and TGFbeta1, -2, and -3. We propose that VMPCs are a good model of specialized mesenchyme involved in prostatic organogenesis and are distinct from general urogenital sinus mesenchyme/stroma. Treatment of VMPCs with TGFbeta1 resulted in a rapid and transient decrease in Fgf10 transcript levels, which were reduced 9-fold at 3 h. TGFbeta1 also inhibited Fgf10 expression in VMP organ rudiments grown in vitro. To further analyze Fgf10 regulation, 6 kb of mouse genomic sequence 5' to the translation start site was characterized by promoter analysis. Deletion analysis of the Fgf10 promoter in VMPCs identified a region of the promoter that mediated a significant proportion of promoter activity as well as mediating promoter down-regulation by TGFbeta1. This element was located between nucleotides -182 and -172 and contained a consensus Sp1 binding site. Taken together, our data suggest that TGFbeta1 is a regulator of Fgf10 expression in prostatic mesenchyme and that a proximal element within the Fgf10 promoter plays an important role in its regulation and expression.

Nuclear Factor I-C Is Essential for Odontogenic Cell Proliferation and Odontoblast Differentiation during Tooth Root Development

“…In the present study, Nfic-deficient primary pulp cells were shown to express a decreased level of Fgf10 compared with wild type cells. Recently, it has been reported that TGF-␤1 down-regulates Fgf10 in the lung (40) and the prostate (41). Likewise, Nfic-deficient primary pulp cells showed a decrease in proliferation activity in vitro when compared with control cells.…”

Uninephrectomy reduces 11β-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats

“…Thus, time-course studies after UNX in the remaining kidney must be performed in order to identify relevant regulatory factors for the expression of 11b-HSD1 and 11b-HSD2. A number of factors regulating the expression of 11b-HSD enzymes have previously been identified including TNF-a, Erg1, NF-kB, NF1, C/EBPs, GR, Sp1/Sp3, Arnt, PPAR-a/PPAR-g, IL1, glucocorticoids, sex steroids, and thyroid hormones (Alikhani-Koopaei et al 2004, Tomlinson et al 2004, Kostadinova et al 2005, Alikhani-Koupaei et al 2007, Wake et al 2007, Ignatova et al 2009). The ultimate proof for a pivotal relevance of one or a combination of these factors would require the investigation of animals with specific over-or under-expression in the cortical collecting duct.…”

Mesodermal Deletion of Transforming Growth Factor-β Receptor II Disrupts Lung Epithelial Morphogenesis

“…Activation of TGF-␤ in mesenchymal cells markedly inhibits Fgf10 expression (37,43,44). Positive transcriptional regulators of Fgf10, Tbx4, and Foxf1 are controlled by Shh signaling that emanates from the branching epithelium.…”