title: Regulation of Prostate Development and Benign Prostatic Hyperplasia by Autocrine Cholinergic Signaling via Maintaining the Epithelial Progenitor Cells in Proliferating Status.
abstract: Regulation of prostate epithelial progenitor cells is important in prostate development and prostate diseases. Our previous study demonstrated a function of autocrine cholinergic signaling (ACS) in promoting prostate cancer growth and castration resistance. However, whether or not such ACS also plays a role in prostate development is unknown. Here, we report that ACS promoted the proliferation and inhibited the differentiation of prostate epithelial progenitor cells in organotypic cultures. These results were confirmed by ex vivo lineage tracing assays and in vivo renal capsule recombination assays. Moreover, we found that M3 cholinergic receptor (CHRM3) was upregulated in a large subset of benign prostatic hyperplasia (BPH) tissues compared with normal tissues. Activation of CHRM3 also promoted the proliferation of BPH cells. Together, our findings identify a role of ACS in maintaining prostate epithelial progenitor cells in the proliferating state, and blockade of ACS may have clinical implications for the management of BPH.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Naitao
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Bai-Jun
authors.initials: BJ
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Quan
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: yangru@yahoo.com.
authors.forename: Ru
authors.initials: R
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China; Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: gao.weiqiang@sjtu.edu.cn.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043587:Receptor, Muscarinic M3 / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D043587:Receptor, Muscarinic M3
keywords: BPH; CHRM3; autocrine cholinergic signaling; epithelial progenitor cells; prostatic branching morphogenesis