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Mol Med. 2018 Nov 27;24(1):60. doi: 10.1186/s10020-018-0062-1.

Extracorporeal shockwave against inflammation mediated by GPR120 receptor in cyclophosphamide-induced rat cystitis model.

Chen YL1,2,3,4, Lin YP2, Sun CK5, Huang TH1,3,4, Yip HK6,7,8,9,10, Chen YT11,12.

Author information

1
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong District, Kaohsiung, 83301, Taiwan.
2
Department of health and Beauty, Shu-Zen Junior College of Medicine and Management, No.452, Huanqiu Rd. Luzhu Dist., Kaohsiung, 82144, Taiwan.
3
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan.
4
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan.
5
Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, No. 1, Yi-Da Road, Jiao-Su Village, Yan-Chao District, Kaohsiung, 82445, Taiwan.
6
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong District, Kaohsiung, 83301, Taiwan. han.gung@msa.hinet.net.
7
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan. han.gung@msa.hinet.net.
8
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan. han.gung@msa.hinet.net.
9
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan. han.gung@msa.hinet.net.
10
Department of Nursing, Asia University, Taichung, 41354, Taiwan. han.gung@msa.hinet.net.
11
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan. yenta1965@gmail.com.
12
Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road, Niaosong District, Kaohsiung, 83301, Taiwan. yenta1965@gmail.com.

Abstract

BACKGROUND:

We tested the hypothesis that extracorporeal shockwave treatment (ESWT) can abolish inflammation and restore urothelial barrier integrity in acute interstitial cystitis by upregulating the fatty acid receptor GPR120.

METHODS:

A total of 30 female Sprague-Dawley rats were categorized into five groups: (1) sham-operated rats (SC); (2) rats treated with ESWT (SC + ESWT); (3) rats with bladder irritation using 150 mg/kg cyclophosphamide through intraperitoneal injection; (4) cyclophosphamide rats treated with ESWT (cyclophosphamide+ESWT); (5) cyclophosphamide rats treated with GPR120 agonist (cyclophosphamide+GW9508).

RESULTS:

On Day 3, urine and bladder specimens were collected for biochemical, histopathological, immunological, and immunoblotting analysis. Following stimulation with cyclophosphamide, the inhibition of the elevated levels of TAK1/NF-κB and phospho-TAK1/NF-κB by ESWT and GPR120 agonists in RT4 cells was associated with a suppression of NF-κB translocation from the cytosol to the nucleus. Accordingly, this anti-inflammatory effect was abolished by GPR120 antagonist and knockdown of GPR120. Histologically, bladder inflammation in cyclophosphamide-treated rats was suppressed by GW9508 or ESWT. Masson's trichrome and Sirius red staining revealed that cyclophosphamide treatment enhanced synthesis of extracellular matrix in rats that was reversed by GW9508 or ESWT. Upregulated pro-inflammatory mediators and cytokines in the cyclophosphamide-treated rats were also suppressed in the GW9508- or ESWT-treated rats. The significantly increased inflammatory cell infiltration as well as the impaired urothelial integrity of the bladder after cyclophosphamide treatment were reversed by treatment with GW9508 or ESWT.

CONCLUSIONS:

These findings suggest that GPR120, the sensing receptor for ESWT, may be useful in the treatment of interstitial cystitis by inhibiting inflammatory response in bladder cells.

KEYWORDS:

Extracorporeal shockwave treatment; GPR120; Inflammation; Interstitial cystitis

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