Paper - WANFANG MED ONLINE

You Position: Home > Paper

The sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy

( views:0, downloads:0 )

Author:: No author available

Journal Title:: Chinese Medical Journal

Issue:: 10

DOI:: 10.1097/CM9.0000000000000767

Key Word:: Myosin light chains;Ovariectomy;Rats;Rho-associated kinases;Sphingosine-1-phosphate;Urinary bladder;Myosin light chains;Ovariectomy;Rats;Rho-associated kinases;Sphingosine-1-phosphate;Urinary bladder

Abstract： Background::Dysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.Methods::Thirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance.Results::The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P < 0.05), S1P (21.73 ± 1.09 nmol/g vs. 18.86 ± 0.69 nmol/g) ( P < 0.05), and S1P receptor 2/3 (S1PR2/3) (mRNA: 25%, 27%, respectively) ( P < 0.05). However, the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups ( P > 0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P < 0.05), p-MYPT1 (protein: 54%) ( P < 0.05), and p-MLC20 (protein: 47%) ( P < 0.05), but there were no significant differences in the mRNA and protein levels of RhoA, ROCK1, MYPT1, and MLC20 (all P > 0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05). Conclusion::In this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

Reference

[1]Taís Silveira,Assmann,Fermín I,Milagro,José Alfredo,Martínez.Crosstalk between microRNAs, the putative target genes and the lncRNA network in metabolic diseases.[J].2019,20(4).
[2]Meng, Su,Jian, Zhao,Yan, Xiaofei,etc.LncRNA SNHG6 inhibits cell proliferation and metastasis by targeting ETS1 via the PI3K/AKT/mTOR pathway in colorectal cancer[J].2019,20(3 Pt.B).
[3].Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma.[J].2017.
[4]Xin,Zhu,Guangling,Yang,Jisheng,Xu,etc.Silencing of SNHG6 induced cell autophagy by targeting miR-26a-5p/ULK1 signaling pathway in human osteosarcoma.[J].2019,19.
[5]Neoptolemos JP,Costello E.Pancreatic cancer in 2010: New insights for early intervention and detection.[J].2011,8(2).
[6]Lv, Pengwei,Qiu, Xinguang,Gu, Yuanting,etc.Long non-coding RNA SNHG6 enhances cell proliferation, migration and invasion by regulating miR-26a-5p/MAPK6 in breast cancer[J].2019,110.
[7]Liang, Rui,Xiao, Guodong,Wang, Meng,etc.SNHG6 functions as a competing endogenous RNA to regulate E2F7 expression by sponging miR-26a-5p in lung adenocarcinoma[J].2018,107.
[8]Zhang, Ji-Jun,Jia, Jie-peng,Shao, Quan,etc.Diabetes mellitus and risk of pancreatic cancer in China: A meta-analysis based on 26 case-control studies[J].2019,13(3).
[9]Sun, Y.,Wei, G.,Luo, H.,etc.The long noncoding RNA SNHG1 promotes tumor growth through regulating transcription of both local and distal genes[J].2017,36(49).
[10]Deng, Jingjing,He, Miaoxia,Chen, Lizao,etc.The Loss of miR-26a-Mediated Post-Transcriptional Regulation of Cyclin E2 in Pancreatic Cancer Cell Proliferation and Decreased Patient Survival.[J].2013,8(10).
[11]Hui, Qian,Chen, Yang,Yixin, Yang.MicroRNA-26a inhibits the growth and invasiveness of malignant melanoma and directly targets on MITF gene.[J].2017,3(Spec ).
[12]Hoang Van T.,Verma Divij,Godavarthy Parimala Sonika,etc.The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia[J].2019,33(7).
[13]Yan, Xiaohui,Hu, Zhongyi,Feng, Yi,etc.Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers[J].2015,28(4).
[14]Zi-Ming,Huang,Heng-Fa,Ge,Chen-Chen,Yang,etc.MicroRNA-26a-5p inhibits breast cancer cell growth by suppressing RNF6 expression.[J].2019.
[15]Venturutti, L.,Russo, R. I. Cordo,Rivas, M. A.,etc.MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1[J].2016,35(48).
[16]Dongliang,Shi,Haiyan,Wang,Mingjian,Ding,etc.MicroRNA-26a-5p inhibits proliferation, invasion and metastasis by repressing the expression of Wnt5a in papillary thyroid carcinoma.[J].2019,12.
[17]Mingyuan Zhang,Wenbiao Duan,Weiliang Sun.LncRNA SNHG6 promotes the migration, invasion, and epithelial-mesenchymal transition of colorectal cancer cells by miR-26a\/EZH2 axis[J].2019,12.
[18]Y.-H. YUAN,J. ZHOU,Y. ZHANG,etc.Identification of key genes and pathways downstream of the beta-catenin-TCF7Ll complex in pancreatic cancer cells using bioinformatics analysis.[J].2019,18(2 Pt.A).
[19]Debaize, Lydie,Troadec, Marie-Berengere.The master regulator FUBP1: its emerging role in normal cell function and malignant development[J].2019,76(2).
[20]Yang Zhang,Danyi Zhao,Lei Song.MiR-16-1 Targeted Silences Far Upstream Element Binding Protein 1 to Advance the Chemosensitivity to Adriamycin in Gastric Cancer[J].2018,24(3).
[21].Construction and analysis for differentially expressed long non-coding RNAs and MicroRNAs mediated competing endogenous RNA network in colon cancer.[J].2018,13(2).
[22]Kamisawa, Terumi,Wood, Laura D.,Itoi, Takao,etc.Pancreatic cancer[J].2016,388(10039).
[23]Hai Wen,Hong Ma,Pengzhi Li,etc.Expression of far upstream element-binding protein 1 correlates with c-Myc expression in sacral chordomas and is associated with tumor progression and poor prognosis[J].2017,491(4).
[24]Yong Wu,Yu Deng,Qinhao Guo,etc.Long non‐coding RNA SNHG6 promotes cell proliferation and migration through sponging miR‐4465 in ovarian clear cell carcinoma[J].2019,23(8).
[25]Gao, Jun,Zeng, Kang,Liu, Yi,etc.LncRNA SNHG5 promotes growth and invasion in melanoma by regulating the miR-26a-5p/TRPC3 pathway.[J].2019,12.
[26]Batchu, Ramesh B.,Gruzdyn, Oksana V.,Qazi, Aamer M.,etc.Enhanced phosphorylation of p53 by microRNA-26a leading to growth inhibition of pancreatic cancer[J].2015,158(4).
[27]Biankin Andrew V.,Waddell Nicola,Kassahn Karin S.,etc.Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes[J].2012,491(7424).
[28]Saleh,H.,Philip,P.A.,Sarkar,F.H.,etc.MicroRNA profiling of diagnostic needle aspirates from patients with pancreatic cancer[J].2012,107(8).
[29]Seki, N.,Yonemori, M.,Enokida, H.,etc.Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer[J].2016,115(3).
[30]Weifeng, Song,Qi, Li,Lei, Wang,etc.Modulation of FoxO1 expression by miR-21 to promote growth of pancreatic ductal adenocarcinoma.[J].2015,35.
[31]Limin Su,Aiying Wu,Weitong Zhang,etc.Silencing long non-coding RNA SNHG6 restrains proliferation, migration and invasion of Wilms’ tumour cell lines by regulating miR-15a[J].2019,47(1).