Transforming Growth Factor Beta 1 Impairs Benign Prostatic Luminal Epithelial Cell Monolayer Barrier Function

Overview

Journal Am J Clin Exp Urol

Specialty Urology

Date 2020 Mar 27

PMID 32211449

Citations 10

Authors

Feng Li

Laura E Pascal

Ke Wang

Yibin Zhou

Goundappa K Balasubramani

Katherine J OMalley

Rajiv Dhir

Kai He

Donna Stolz

Donald B DeFranco

Naoki Yoshimura

Joel B Nelson

Tie Chong

Peng Guo

Dalin He

Zhou Wang

Affiliations

Soon will be listed here.

Abstract

Our recent studies identifying the presence of luminal secretory protein PSA in the stroma, decreased E-cadherin expression, and reduced number of tight junction kiss points in benign prostatic hyperplasia (BPH) tissues suggest that epithelial barrier permeability is increased in BPH. However, the cause of increased epithelial permeability in BPH is unclear. Transforming growth factor beta 1 (TGF-β1) has been reported to be up-regulated in clinical BPH specimens and TGF-β1 overexpression induced fibrosis and inflammation in a murine model. TGF-β1 was reported to repress the expression of E-cadherin in benign prostatic cells. However, whether and how TGF-β1 up-regulation affects epithelial barrier permeability is unknown. Here, benign prostatic epithelial cell lines BHPrE1 and BPH-1 were utilized to determine the impact of TGF-β1 treatment on epithelial barrier, tight junctions, and expression of E-cadherin and claudin 1 by transepithelial electrical resistance (TEER) measurement, FITC-dextran trans-well diffusion assays, qPCR, as well as transmission electron microscopy (TEM) observation. Laser capture micro-dissection (LCM) combined with reverse transcription-polymerase chain reaction (qPCR) were utilized to determine the expression of E-cadherin and claudin 1 in BPH patient specimens. TGF-β1 treatment decreased TEER, increased FITC-dextran diffusion, and reduced the mRNA expression of junction protein claudin 1 in cultured cell monolayers. Claudin 1 mRNA but not E-cadherin mRNA was down-regulated in the luminal epithelial cells in BPH nodules compared to normal prostate tissues. Our studies suggest that TGF-β1 could increase the permeability through decreasing the expression of claudin 1 and inhibiting the formation of tight junctions in BHPrE1 and BPH-1 monolayers. These results suggest that TGF-β1 might play an important role in BPH pathogenesis through increasing the permeability of luminal epithelial barrier in the prostate.

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References

Hu S, Yu W, Lv T, Chang C, Li X, Jin J . Evidence of TGF-β1 mediated epithelial-mesenchymal transition in immortalized benign prostatic hyperplasia cells. Mol Membr Biol. 2014; 31(2-3):103-10. DOI: 10.3109/09687688.2014.894211. View

Liu T, Grubisha M, Frahm K, Wendell S, Liu J, Ricke W . Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor β (ERβ) Response to 5α-Reductase Inhibition in Prostate Epithelial Cells. J Biol Chem. 2016; 291(28):14747-60. PMC: 4938192. DOI: 10.1074/jbc.M115.711515. View

Zhang K, Zhang H, Xiang H, Liu J, Liu Y, Zhang X . TGF-β1 induces the dissolution of tight junctions in human renal proximal tubular cells: role of the RhoA/ROCK signaling pathway. Int J Mol Med. 2013; 32(2):464-8. DOI: 10.3892/ijmm.2013.1396. View

Slabakova E, Pernicova Z, Slavickova E, Starsichova A, Kozubik A, Soucek K . TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Prostate. 2011; 71(12):1332-43. DOI: 10.1002/pros.21350. View

Jiang M, Strand D, Fernandez S, He Y, Yi Y, Birbach A . Functional remodeling of benign human prostatic tissues in vivo by spontaneously immortalized progenitor and intermediate cells. Stem Cells. 2009; 28(2):344-56. PMC: 2962907. DOI: 10.1002/stem.284. View

OMalley K, Dhir R, Nelson J, Bost J, Lin Y, Wang Z . The expression of androgen-responsive genes is up-regulated in the epithelia of benign prostatic hyperplasia. Prostate. 2009; 69(16):1716-23. PMC: 2804845. DOI: 10.1002/pros.21034. View

Marchiando A, Graham W, Turner J . Epithelial barriers in homeostasis and disease. Annu Rev Pathol. 2010; 5:119-44. DOI: 10.1146/annurev.pathol.4.110807.092135. View

Li F, Ma Z, Guan Z, Chen Y, Wu K, Guo P . Autophagy induction by silibinin positively contributes to its anti-metastatic capacity via AMPK/mTOR pathway in renal cell carcinoma. Int J Mol Sci. 2015; 16(4):8415-29. PMC: 4425089. DOI: 10.3390/ijms16048415. View

Descazeaud A, Rubin M, Hofer M, Setlur S, Nikolaief N, Vacherot F . BPH gene expression profile associated to prostate gland volume. Diagn Mol Pathol. 2008; 17(4):207-13. PMC: 2822796. DOI: 10.1097/PDM.0b013e31816f6352. View

10.

Noth R, Stuber E, Hasler R, Nikolaus S, Kuhbacher T, Hampe J . Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease. J Crohns Colitis. 2012; 6(4):464-9. DOI: 10.1016/j.crohns.2011.10.004. View

11.

Funahashi Y, Wang Z, OMalley K, Tyagi P, DeFranco D, Gingrich J . Influence of E. coli-induced prostatic inflammation on expression of androgen-responsive genes and transforming growth factor beta 1 cascade genes in rats. Prostate. 2014; 75(4):381-9. PMC: 4293351. DOI: 10.1002/pros.22924. View

12.

Alonso-Magdalena P, Brossner C, Reiner A, Cheng G, Sugiyama N, Warner M . A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia. Proc Natl Acad Sci U S A. 2009; 106(8):2859-63. PMC: 2650376. DOI: 10.1073/pnas.0812666106. View

13.

Martinez-Estrada O, Culleres A, Soriano F, Peinado H, Bolos V, Martinez F . The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells. Biochem J. 2005; 394(Pt 2):449-57. PMC: 1408675. DOI: 10.1042/BJ20050591. View

14.

Li F, Pascal L, Stolz D, Wang K, Zhou Y, Chen W . E-cadherin is downregulated in benign prostatic hyperplasia and required for tight junction formation and permeability barrier in the prostatic epithelial cell monolayer. Prostate. 2019; 79(11):1226-1237. PMC: 6599563. DOI: 10.1002/pros.23806. View

15.

Youn D, Park J, Kim H, Jung Y, Kang J, Jeong M . Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase. Oncotarget. 2016; 8(6):9500-9512. PMC: 5354748. DOI: 10.18632/oncotarget.13430. View

16.

Georas S, Rezaee F . Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol. 2014; 134(3):509-20. PMC: 4170838. DOI: 10.1016/j.jaci.2014.05.049. View

17.

Pierucci-Alves F, Yi S, Schultz B . Transforming growth factor beta 1 induces tight junction disruptions and loss of transepithelial resistance across porcine vas deferens epithelial cells. Biol Reprod. 2011; 86(2):36. PMC: 3290666. DOI: 10.1095/biolreprod.111.092262. View

18.

Deschenes-Simard X, Gaumont-Leclerc M, Bourdeau V, Lessard F, Moiseeva O, Forest V . Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation. Genes Dev. 2013; 27(8):900-15. PMC: 3650227. DOI: 10.1101/gad.203984.112. View

19.

Fakhoury M, Negrulj R, Mooranian A, Al-Salami H . Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res. 2014; 7:113-20. PMC: 4106026. DOI: 10.2147/JIR.S65979. View

20.

Funahashi Y, OMalley K, Kawamorita N, Tyagi P, DeFranco D, Takahashi R . Upregulation of androgen-responsive genes and transforming growth factor-β1 cascade genes in a rat model of non-bacterial prostatic inflammation. Prostate. 2014; 74(4):337-45. PMC: 3898594. DOI: 10.1002/pros.22668. View