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Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis

Publication: Research - peer-reviewJournal article

S B Winge, J Nielsen, Anders Jørgensen, Sylwia Owczarek Jacobsen, K A Ewen, J E Nielsen, Anders Juul, V Berezin, Ewa Rajpert-De Meyts

Regulation of spermatogonial maintenance in the human testis is currently not well understood. One pathway suggested to be involved is activated by fibroblast growth factor receptor 3 (FGFR3), which is expressed in a subset of spermatogonia. FGFR3-activating mutations have been identified in spermatocytic seminoma, thought to originate from clonal expansion of spermatogonia. In this study we aimed to characterize potential binding partners of FGFR3, and specifically its mesenchymal "c" splice isoform, in human spermatogonia. Based on expression patterns and homology to the binding site, we identified FGF1, FGF2, and FGF9 as the best candidates for natural ligands of FGFR3c in the testis. In addition, we screened non-FGF proteins and found that a proteoglycan biglycan (BGN) contains a sequence homologous to the FGFR3c binding site on FGF1, and is expressed in peritubular cells adjacent to FGFR3-expressing spermatogonia. Experiments in a cell-free system confirmed that BGN binds to FGFR3c and FGF1. In conclusion, our findings further clarify the complex regulation of FGFR3c in the human testis. We postulate that BGN is a factor secreted by peritubular cells to modulate FGFR3c signaling and thus contributes to the regulation of spermatogonial maintenance.

Original languageEnglish
JournalMolecular and cellular endocrinology
Volume399
Pages (from-to)235-43
Number of pages9
ISSN0303-7207
DOIs
StatePublished - Jan 2015

ID: 137365992