Androgen Indirectly Regulates Gap Junction Component Connexin 43 Through Wilms Tumor-1 in Sertoli Cells

2020 ◽  
Vol 29 (3) ◽  
pp. 169-176 ◽  
Author(s):  
Qin Xia ◽  
Danchen Zhang ◽  
Jingjing Wang ◽  
Xiaoyu Zhang ◽  
Weixiang Song ◽  
...  
Keyword(s):  
Gap Junction ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Wilms Tumor ◽  
Wilms Tumor 1

scholarly journals Androgen Promotes Differentiation of PLZF+ Spermatogonia pool via Indirect Regulatory Pattern

2018 ◽  
Author(s):  
Jingjing Wang ◽  
Jinmei Li ◽  
Yunzhao Gu ◽  
Qin Xia ◽  
Weixiang Song ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Culture System ◽  
Molecular Mechanisms ◽  
Wilms Tumor ◽  
Post Partum ◽  
Mice Model ◽  
Androgen Action ◽  
Wilms Tumor 1

AbstractAndrogen signaling plays a pivotal role in spermatogenesis, but the molecular mechanisms underlying androgen action in this process are unclear. Specifically, it is unknown if the androgen receptor (AR) is expressed in germ cells. Thus it’s interesting to reveal how androgen induces differentiation of spermatogonial progenitor cells (SPCs) in the niche. Here we observed the AR is primarily expressed in pre-spermatogonia of mice 2 days post partum (dpp), absent before spermatogenesis onset, and then expressed in surrounding Sertoli cells. Then we examined a regulatory role of the AR in spermatogenesis using a SPCs-Sertoli cells co-culture system, and demonstrated that androgen negatively regulated Plzf (the gene for stemness maintenance of SPCs). Additionally, we identified Gata2 as a target of AR in Sertoli cells, and demonstrated that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer differentiation signals to SPCs, which was further verified using androgen pharmacological-deprivation mice model. These results demonstrate a regulatory pattern of androgen in SPCs niche in an indirect way via multiple steps of signal transduction.

scholarly journals Intercellular calcium signaling via gap junction in connexin-43-transfected cells.

1998 ◽  
Vol 273 (35) ◽  
pp. 22856
Author(s):  
Toshihiko Toyofuku ◽  
Masanori Yabuki ◽  
Kinya Otsu ◽  
Tsunehiko Kuzuya ◽  
Masatsugu Hori ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Gap Junction ◽  
Connexin 43 ◽  
Transfected Cells

scholarly journals Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

2015 ◽  
Vol 123 (4) ◽  
pp. 989-997 ◽  
Author(s):  
Keiichi Sakai ◽  
Shigetaka Shimodaira ◽  
Shinya Maejima ◽  
Nobuyuki Udagawa ◽  
Kenji Sano ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Malignant Glioma ◽  
Stable Disease ◽  
Wilms Tumor ◽  
Malignant Gliomas ◽  
Tumor Lysate ◽  
Dc Vaccine ◽  
Pulsed Dc ◽  
Wilms Tumor 1 ◽  
Vaccination Therapy

OBJECT Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms’ tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. METHODS WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 107 to 2 × 107 pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5–7 sessions (1 course) during an individual chemotherapy regimen. RESULTS Ten patients (3 men, 7 women; age range 24–64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide–pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate–pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1–2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. CONCLUSIONS This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.

scholarly journals Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Mayur Choudhary ◽  
Christine Naczki ◽  
Wenhong Chen ◽  
Keith D. Barlow ◽  
L. Douglas Case ◽  
...  
Keyword(s):  
Gap Junction ◽  
Connexin 43 ◽  
Endothelial Proliferation
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