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Effect of TGF-β/Smad signaling on sertoli cell and possible mechanism related to complete sertoli cell-only syndrome

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Abstract

The roles of TGF-β and the interaction between TGF-β and EGFR signaling are critical in Sertoli cell, though the knowledge about them is limited. RT-PCR was used to characterize the status of TGF-β signaling in clinical testicular specimens with complete Sertoli cell-only syndrome (SCOS). The mouse Sertoli cell TM4 was used to investigate the interaction between TGF-β and EGFR signaling by using mitogenic assay, luciferase assay, and western blot, while TM3 (mouse leydig cell), 3T3 (mouse embryo fibroblasts), and B82 (mouse lung fibroblasts) were selected as control. The RT-PCR assay indicated that the expression levels of TβRII and Smad2 in SCOS testes were upregulated compared to that in the normal controls. In the in vitro experiment, the TGF-β1 downregulated cellular proliferation of TM3 and B82 cell (P < 0.05), but it did not changed the proliferation of TM4 and 3T3 cells (P > 0.05). On contrast, TGF-β1 only increased the TGF response elements p3TP-lux activity significantly (P < 0.05) in Sertoli cell TM4. Also, the Western blot assay shows an obvious increase of Smad2 in TM4, 3T3, and TM3 cells after TGF-β1 treatment while the EGFR expression level was significantly increased in TM4 cells only. In conclusion, the TGF-β pathway and the cross-link between TGF-β and EGFR signaling may play an important role on the dysfunction of Sertoli cells which induce germ stem cells’ disappearance in SCOS.

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Abbreviations

SCOS:

Sertoli cell-only syndrome

TGF-β:

Transforming growth factor β

TβRI:

Transforming growth factor β receptor I

TβRII:

Transforming growth factor β receptor II

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

RTK:

Receptor tyrosine kinase

LH:

Luteotrophic hormone

FSH:

Follicle-stimulating hormone

NOA:

Non-obstructive azoospermia

MAPK:

Mitogen-activated protein kinase

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Acknowledgments

This work was supported by CNSF 211 Project #No. 219. and CNSF No.30772285

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Authors and Affiliations

  1. Andrology Center, Peking University First Hospital, Peking University, No. A59, Di’anmen West Street, Xicheng District, Beijing, 100009, People’s Republic of China

    Tao Sun, Zhongcheng Xin, Zhe Jin, Yiguang Wu & Yanqing Gong

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  1. Tao Sun
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  2. Zhongcheng Xin
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  3. Zhe Jin
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Correspondence to Zhongcheng Xin.

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Sun, T., Xin, Z., Jin, Z. et al. Effect of TGF-β/Smad signaling on sertoli cell and possible mechanism related to complete sertoli cell-only syndrome. Mol Cell Biochem 319, 1–7 (2008). https://doi.org/10.1007/s11010-008-9869-3

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