Integrin αv Mediates Contractility Whereas Integrin α4 Regulates Proliferation of Human Bladder Smooth Muscle Cells via FAK Pathway under Physiological Stretch

Luo, Deyi; Wazir, Romel; Tian, Ye; Yue, Xuan; Wei, Tangqiang; Wang, Kun‐Jie

doi:10.1016/j.juro.2013.04.027

Cited by 28 publications

(35 citation statements)

References 28 publications

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“…FAK acts as an upstream regulator of ERK1/2 signaling under conditions of mechanical stimulation in many non-chondrocytic cell types [13,14]. Various studies have demonstrated a pivotal role of FAK in integrin-mediated signal transduction pathways in different cell types [15,16,17]. Although interactions of FAK and Src within signal transduction pathways in different non-chondrocytic cell types have been extensively analyzed, the conclusions are controversial [10,18].…”

Section: Introductionmentioning

confidence: 99%

Periodic Mechanical Stress Stimulates the FAK Mitogenic Signal in Rat Chondrocytes Through ERK1/2 Activity

Liang

Ren

Liu

et al. 2013

Cell Physiol Biochem

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Background/Aims: The biological effects of periodic mechanical stress on chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying chondrocyte mechanosensing and signaling in response to periodic mechanical stress remain to be determined. In the current study, we examined the effects of focal adhesion kinase (FAK) signaling on periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. Methods and Results: Periodic mechanical stress significantly induced sustained phosphorylation of FAK at Tyr³⁹⁷ and Tyr^576/577. Reduction of FAK with targeted shRNA via transfection of NH₂-terminal tyrosine phosphorylation-deficient FAK mutant Y397F or Y576F-Y577F abolished periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis, accompanied by attenuated ERK1/2 phosphorylation. However, activation of Src, PLCγ1 and Rac1 was not prevented upon FAK suppression. Furthermore, pretreatment with the Src-selective inhibitor, PP2, and shRNA targeted to Src or suppression of Rac1 with its selective inhibitor, NSC23766, blocked FAK phosphorylation at Tyr,^576/577 but not Tyr,³⁹⁷ under periodic mechanical stress. Interestingly, FAK phosphorylation neither at Tyr³⁹⁷ nor at Tyr^576/577 was affected by PLCγ1 depletion when periodic mechanical stress was applied. In addition, Tyr³⁹⁷ and Tyr^576/577 phosphorylation levels were reduced upon pretreatment with a blocking antibody against integrin β1 under conditions of periodic mechanical stress. Conclusion: Our findings collectively suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis through at least two pathways, integrin β1-Src-Rac1-FAK(Tyr^576/577)-ERK1/2 and integrin β1-FAK (Tyr³⁹⁷)-ERK1/2.

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Section: Introductionmentioning

confidence: 99%

Periodic Mechanical Stress Stimulates the FAK Mitogenic Signal in Rat Chondrocytes Through ERK1/2 Activity

Liang

Ren

Liu

et al. 2013

Cell Physiol Biochem

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“…The role of FAK for nonprostatic smooth muscle contractility has previously been studied using cultured bladder smooth muscle cells and isolated airway smooth muscle from dogs (21,39). In contrast, the involvement of FAK in the regulation of contractility has, to the best of our knowledge, not been addressed in intact human smooth muscle preparations.…”

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confidence: 99%

Inhibition of smooth muscle force generation by focal adhesion kinase inhibitors in the hyperplastic human prostate

Kunit

Gratzke

Schreiber

et al. 2014

American Journal of Physiology-Renal Physiology

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Smooth muscle contraction may be critical for lower urinary tract symptoms (LUTS) in patients with benign prostate hyperplasia and requires stable anchorage of the cytoskeleton to the cell membrane. These connections are regulated by focal adhesion kinase (FAK). Here, we addressed the involvement of FAK in the regulation of smooth muscle contraction in hyperplastic human prostate tissues. Prostate tissues were obtained from radical prostatectomy. Expression of FAK and focal adhesion proteins was assessed by Western blot analysis and immunohistochemical stainings. Effects of the FAK inhibitors PF-573228 and Y-11 on contraction of prostate strips were examined in the organ bath. Expression of FAK and focal adhesion proteins (integrin-5α, paxilin, and c-Src) was detected by Western blot analysis in prostate samples. By double immunofluorescence staining with calponin and pan-cytokeratin, expression of FAK was observed in stromal and epithelial cells. Immunoreactivity for FAK colocalized with integrin-5α, paxilin, talin, and c-Src. Stimulation of prostate tissues with the α1-adrenergic agonist phenylephrine increased the phosphorylation state of FAK at Tyr³⁹⁷ and Tyr⁹²⁵ with different kinetics, which was blocked by the α1-adrenoceptor antagonist tamsulosin. Norepinephrine and phenylephrine induced concentration-dependent contractions of prostate strips. Both FAK inhibitors PF-573228 and Y-11 significantly inhibited norepinephrine- and phenylephrine-induced contractions. Finally, PF-573228 and Y-11 inhibited contractions induced by electric field stimulation, which was significant at the highest frequency. In conclusion, α1-adrenergic smooth muscle contraction or its regulation involves FAK in the human prostate. Consequently, FAK may be involved in the pathophysiology of LUTS and in current or future LUTS therapies.

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“…Our earlier findings showed that simulated physiological stretch could induce proliferation of HBSMCs through several signaling pathways [11,28]. However, microenvironment changes that affect cell behaviors of HBSMCs under physiological stretch are not well understood.…”

Section: Discussionmentioning

confidence: 98%

“…Additionally, we recently observed that physiological stretch also increased HBSMCs contractility by examining the percentage of retraction of the collagen gel reaction [11], and this increased contractility was also regulated by MMPs activity [19].…”

Section: Introductionmentioning

confidence: 95%

“…Previous studies showed that both hydrodynamic pressure and stretch can stimulate HBSMCs proliferation and viability in a certain range, while stress exceeded the limits, these biological behaviors of HBSMCs would be restrained [9][10][11]. In this mechanical parameters-depended dynamic process, HBSMCs behaviors are influenced by several factors, including activation of signaling pathways and alteration of cellular morphology.…”

Section: Introductionmentioning

confidence: 99%

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Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs

Zhu

Peng

et al. 2014

Archives of Biochemistry and Biophysics

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Integrin αv Mediates Contractility Whereas Integrin α4 Regulates Proliferation of Human Bladder Smooth Muscle Cells via FAK Pathway under Physiological Stretch

Cited by 28 publications

References 28 publications

Periodic Mechanical Stress Stimulates the FAK Mitogenic Signal in Rat Chondrocytes Through ERK1/2 Activity

Periodic Mechanical Stress Stimulates the FAK Mitogenic Signal in Rat Chondrocytes Through ERK1/2 Activity

Inhibition of smooth muscle force generation by focal adhesion kinase inhibitors in the hyperplastic human prostate

Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs

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