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01-08-2017 | Original Article

Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway

Authors: Shulian Chen, Chuandu Peng, Xin Wei, Deyi Luo, Yifei Lin, Tongxin Yang, Xi Jin, Lina Gong, Hong Li, Kunjie Wang

Published in: World Journal of Urology | Issue 8/2017

Abstract

Objectives

To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs).

Methods

HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection.

Results

The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK.

Conclusion

Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

Mammoto T, Ingber DE (2010) Mechanical control of tissue and organ development. Development 137(9):1407–1420. doi:10.1242/dev.024166 CrossRefPubMedPubMedCentral

Coplen DE, Macarak EJ, Howard PS (2003) Matrix synthesis by bladder smooth muscle cells is modulated by stretch frequency. Vitro Cell Dev Biol Anim 39(3–4):157–162. doi:10.1007/s11626-003-0010-3 CrossRef

Baskin L, Howard PS, Macarak E (1993) Effect of physical forces on bladder smooth muscle and urothelium. J Urol 150(2 Pt 2):601–607CrossRefPubMed

Ramachandran A, Gong EM, Pelton K, Ranpura SA, Mulone M, Seth A et al (2011) FosB regulates stretch-induced expression of extracellular matrix proteins in smooth muscle. Am J Pathol 179(6):2977–2989. doi:10.1016/j.ajpath.2011.08.034 CrossRefPubMedPubMedCentral

Luo D, Wazir R, Tian Y, Yue X, Wei T, Wang K (2013) Integrin αv mediates contractility whereas integrin α4 regulates proliferation of human bladder smooth muscle cells via FAK pathway under physiological stretch. J Urol 190(4):1421–1429. doi:10.1016/j.juro.2013.04.027 CrossRefPubMed

Aitken KJ, Block G, Lorenzo A, Herz D, Sabha N, Dessouki O et al (2006) Mechanotransduction of extracellular signal-regulated kinases 1 and 2 mitogen-activated protein kinase activity in smooth muscle is dependent on the extracellular matrix and regulated by matrix metalloproteinases. Am J Pathol 169(2):459–470. doi:10.2353/ajpath.2006.050969 CrossRefPubMedPubMedCentral

Wu T, Chen L, Wei T, Wang Y, Xu F, Wang K (2012) Effect of cyclic hydrodynamic pressure-induced proliferation of human bladder smooth muscle through Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2. Int J Urol 19(9):867–874. doi:10.1111/j.1442-2042.2012.03043.x CrossRefPubMed

Hsu HJ, Lee CF, Locke A, Vanderzyl SQ, Kaunas R (2010) Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend on mechanical strain rate, but not FAK. PLoS ONE 5(8):e12470. doi:10.1371/journal.pone.0012470 CrossRefPubMedPubMedCentral

Chen L, Wei T, Wang Y, Zhang J, Li H, Wang K (2012) Simulated bladder pressure stimulates human bladder smooth muscle cell proliferation via the PI3K/SGK1 signaling pathway. J Urol 188(2):661–667. doi:10.1016/j.juro.2012.03.112 CrossRefPubMed

10.

Hubschmid U, Leong-Morgenthaler PM, Basset-Dardare A, Ruault S, Frey P (2005) In vitro growth of human urinary tract smooth muscle cells on laminin and collagen type I-coated membranes under static and dynamic conditions. Tissue Eng 11(1–2):161–171. doi:10.1089/ten.2005.11.161 CrossRefPubMed

11.

Chang SL, Howard PS, Koo HP, Macarak EJ (1998) Role of type III collagen in bladder filling. Neurourol Urodyn 17(2):135–145CrossRefPubMed

12.

Gee EP, Ingber DE, Stultz CM (2008) Fibronectin unfolding revisited: modeling cell traction-mediated unfolding of the tenth type-III repeat. PLoS ONE 3(6):e2373. doi:10.1371/journal.pone.0002373 CrossRefPubMedPubMedCentral

13.

Aitken KJ, Bagli DJ (2009) The bladder extracellular matrix. Part I: architecture, development and disease. Nat Rev Urol 6(11):596–611. doi:10.1038/nrurol.2009.201 CrossRefPubMed

14.

Wei W, Howard PS, Kogan B, Macarak EJ (2012) Urinary diversion results in marked decreases in proliferation and apoptosis in fetal bladder. J Urol 188(4):1306–1312. doi:10.1016/j.juro.2012.06.041 CrossRefPubMed

15.

Dozmorov MG, Kropp BP, Hurst RE, Cheng EY, Lin HK (2007) Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder. J Smooth Muscle Res 43(2):55–72CrossRefPubMed

16.

Guan JL (1997) Role of focal adhesion kinase in integrin signaling. Int J Biochem Cell Biol 29(8–9):1085–1096CrossRefPubMed

17.

Schlaepfer DD, Hanks SK, Hunter T, van der Geer P (1994) Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature 372(6508):786–791CrossRefPubMed

18.

Zachary I, Rozengurt E (1992) Focal adhesion kinase (p125FAK): a point of convergence in the action of neuropeptides, integrins, and oncogenes. Cell 71(6):891–894CrossRefPubMed

19.

Laboureau J, Dubertret L, Lebreton-De CC, Coulomb B (2004) ERK activation by mechanical strain is regulated by the small G proteins rac-1 and rhoA. Exp Dermatol 13(2):70–77. doi:10.1111/j.0906-6705.2004.00117.x CrossRefPubMed

Title: Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway
Authors: Shulian Chen
Chuandu Peng
Xin Wei
Deyi Luo
Yifei Lin
Tongxin Yang
Xi Jin
Lina Gong
Hong Li
Kunjie Wang
Publication date: 01-08-2017
Publisher: Springer Berlin Heidelberg
Published in: World Journal of Urology / Issue 8/2017
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-016-1993-1

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Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway

Abstract

Objectives

Methods

Results

Conclusion

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Abstract

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