Distinct expression patterns of Sulf1 and Hs6st1 spatially regulate heparan sulfate sulfation during prostate development.

Distinct expression patterns of Sulf1 and Hs6st1 spatially regulate heparan sulfate sulfation during prostate development.
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DOI:
10.1002/dvdy.23886
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发表时间:
2012-12
影响因子:
2.5
通讯作者:
Marker, Paul C.
Marker, Paul C.
中科院分区:
生物学3区
文献类型:
--
作者:
Buresh-Stiemke, Rita A.;Malinowski, Rita L.;Keil, Kimberly P.;Vezina, Chad M.;Oosterhof, Arie;Van Kuppevelt, Toin H.;Marker, Paul C.

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前列腺形态发生始于泌尿生殖窦 (UGS),伴随上皮芽发育。 Sulfatase-1 (SULF1) 通过减少细胞外硫酸乙酰肝素 (HS) 6-O 硫酸化并通过 ERK1/2 丝裂原激活激酶损害 FGF10 信号传导来抑制芽发育。我们通过原位杂交表征了发育中前列腺中 HS 6-O 硫酸化修饰酶的表达模式,并表明 Sulf1 和 Hs6st1 具有重叠但不同的表达域。值得注意的是,Hs6st1 存在,而 Sulf1 被排除在伸长上皮芽的尖端之外。这预示着在伸长的上皮芽尖端处存在相对较高的 HS 6-O 硫酸化,这一点已通过免疫组织化学得到证实。 Sulf1 在周围间质上皮中的表达模式与 BMP 信号传导的预测位置相匹配。外源性 BMP4 和 BMP7 诱导 UGS 中 Sulf1 的表达,减少上皮 HS 6-O 硫酸化,并减少响应 FGF10 的 ERK1/2 激活。这些数据表明,BMP 至少部分通过诱导 Sulf1 来限制 FGF10 在发育中前列腺中的作用。
Prostate morphogenesis initiates in the urogenital sinus (UGS) with epithelial bud development. Sulfatase-1 (SULF1) inhibits bud development by reducing extracellular heparan sulfate (HS) 6-O sulfation and impairing FGF10 signaling via the ERK1/2 mitogen activated kinases. We characterized the expression patterns of HS 6-O sulfation modifying enzymes in the developing prostate by in situ hybridization and showed that Sulf1 and Hs6st1 had overlapping but distinct expression domains. Notably, Hs6st1 was present while Sulf1 was excluded from the tips of elongating epithelial buds. This predicted relatively high HS 6-O sulfation at the tips of elongating epithelial buds that was confirmed by immunohistochemistry. The pattern of Sulf1 expression in the peri-mesenchymal epithelium matched predicted locations of BMP signaling. Exogenous BMP4 and BMP7 induced Sulf1 expression in the UGS, decreased epithelial HS 6-O sulfation, and reduced ERK1/2 activation in response to FGF10. These data suggest that BMPs limit FGF10 action in the developing prostate at least in part by inducing Sulf1.
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