Expressions of Prostaglandin F2α Receptor and Cyclooxygenase-2 in Tissue of Benign Bile Duct Scar and Their Significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Changen ^1,2 ,  YAO Yingmin ¹ , HAN Shaoshan ¹ , LIU Wantao ¹ , LIU Qingguang. ¹

1.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China;;
2.Department of Endocrine and Vascular Surgery, Affiliated Shiyan People’s Hospital, Yunyang Medical College, Shiyan 442000, Hubei Province, China;

Corresponding author：

YAO Yingmin, Email: yym8181@yahoo.cn

Keywords：

Benign bile duct scar; Prostaglandin F2α receptor; Cyclooxygenase-2; Transforming growth factor-β1

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ObjectiveTo explore the expressions of prostaglandin F2α receptor (PTGFR) and cyclooxygenase-2 (COX-2) in tissues of benign bile duct scar and their significances, and investigate the regulating effect of transforming growth factor-β1 (TGF-β1) on the expression of PTGFR in human bile duct fibroblasts cultured in vitro. MethodsThe samples of common bile duct (CBD) scars were collected from 18 patients with benign bile duct scar stricture and 6 cases of normal CBD tissues from liver transplantation donor were collected as control. The expressions of PTGFR and COX-2 were detected by immunohistochemical strept-avidin-biotin complex (SABC) method. Semiquantitative RT-PCR and ELISA methods were used to detect the mRNA and protein levels of PTGFR in bile duct fibroblasts which were effected by TGF-β1 with different concentrations (0, 10, 20, and 30 ng/ml) for 24 h. ResultsThe positive rates of PTGFR and COX-2 were 88.9% (16/18) and 83.3% (15/18) in tissues of benigh CBD scar and 33.3% (2/6) and 0 (0/6) in normal CBD tissues (P lt;0.05). The expressions of the PTGFR mRNA and protein levels became upregulated when the concentrations of the TGF-β1 became higher in human bile duct fibroblasts (P lt;0.05). And the effect was concentration dependant to some extent. ConclusionsThe high expressions of PTGFR and COX-2 play important roles in the process of benign bile duct stricture formation. TGF-β1 is able to induce higher expressions of PTGFR mRNA level and the PTGFR protein level in a concentration dependent manner, and regulate the formation of benign bile duct stricture.

Citation： LI Changen,YAO Yingmin,HAN Shaoshan,LIU Wantao,LIU Qingguang.. Expressions of Prostaglandin F2α Receptor and Cyclooxygenase-2 in Tissue of Benign Bile Duct Scar and Their Significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(12): 1283-1287. doi: Copy

1.	Oga T, Matsuoka T, Yao C, et al. Prostaglandin F2α receptor signaling facilitates bleomycininduced pulmonary fibrosis independently of transforming growth factorβ [J]. Nat Med, 2009, 15: 14261430.
2.	耿智敏, 向国安, 韩庆, 等. 平滑肌肌动蛋白(SMA)在胆道愈合过程中的表达及意义 [J]. 肝胆外科杂志, 2000, 8(4): 312313.
3.	韩少山, 刘青光, 姚英民, 等. UbcH10在肝细胞癌中的表达及临床病理意义 [J]. 南方医科大学学报, 2011, 31(2): 280284.
4.	Sváb J, Pesková M, Krska Z, et al. Prevention, diagnosis and treatment of iatrogennic lesions of biliary tract during laparoscopic cholecystectomy. Management of papila injury after invasive endoscopy. Part 1. Prevention and diagnosis of bile duct injuries [J]. Rozhl Chir, 2005, 84(4): 176181.
5.	黄志强. 胆管损伤: 肝胆外科永久的议题 [J]. 中华普通外科杂志, 2001, 16(6): 371373.
6.	Geng ZM, Yao YM, Liu QG, et al. Mechanism of benign biliary stricture: a morphological and immunohistochemical study [J]. World J Gastroenterol, 2005, 11(2): 293295.
7.	Prat F, Chapat O, Ducot B, et al. Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline [J]. Gut, 1998, 42(1): 7680.
8.	Sohn TA, Yeo CJ, Cameron JL, et al. Do preoperative biliary stents increase postpancreaticoduodenectomy complications? [J]. J Gastrointest Surg, 2000, 4(3): 258267.
9.	耿智敏, 向国安, 韩庆, 等. 巨噬细胞及转化生长因子β1在肝外胆管损伤修复过程中的表达及其意义 [J]. 中华实验外科杂志, 2000, 17(6): 522523.
10.	耿智敏, 刘青光, 潘承恩, 等. 肌成纤维细胞在胆道愈合过程中的表达及意义 [J]. 中华实验外科杂志, 2001, 18(3): 205206.
11.	耿智敏, 徐军, 刘青光, 等. 良性胆管狭窄形成机制的研究 [J]. 消化外科, 2002, 1(5): 321323.
12.	耿智敏, 向国安, 韩庆, 等. 转化生长因子β1 在胆管愈合过程中的表达及意义 [J]. 中国普外基础与临床杂志, 2000, 7(6): 362363.
13.	Sales KJ, Milne SA, Williams AR, et al. Expression, localization, and signaling of prostaglandin F2α receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogenactivated protein kinase signaling pathways [J]. J Clin Endocrinol Metab, 2004, 89(2): 986993.
14.	Zaragoza DB, Wilson RR, Mitchell BF, et al. The interleukin 1βinduced expression of human prostaglandin F2α receptor messenger RNA in human myometrialderived ULTR cells requires the transcription factor, NFkappaB [J]. Biol Reprod, 2006, 75(5): 697704.
15.	Olman MA. Beyond TGFβ: a prostaglandin promotes fibrosis [J]. Nat Med, 2009, 15(12): 13601361.
16.	梁君蓉, 王新, 吴开春, 等. COX2抑制剂对成纤维细胞的增殖和细胞外基质产生的影响 [J]. 第四军医大学学报, 2004, 25(9): 811814.
17.	Jackson BA, Goldstein RH, Roy R, et al. Effects of transforming growth factor β and interleukin1β on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture [J]. Biochem Biophys Res Commun, 1993, 197(3): 14651474.
18.	Luo J, Lang JA, Miller MW. Transforming growth factor β1 regulates the expression of cyclooxygenase in cultured cortical astrocytes and neurons [J]. J Neurochem, 1998, 71(2): 526534.
19.	Fong CY, Pang L, Holland E, et al. TGFβ1 stimulates IL8 release, COX2 expression, and PGE2 release in human airway smooth muscle cells [J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(1): L201L207.
20.	张小文, 施国明, 邹浩, 等. 良性胆管狭窄瘢痕中CD68、TGFβ1、αSMA的表达 [J]. 中华肝胆外科杂志, 2007, 13(11): 750753.
21.	谢举临, 利天增, 祁少海, 等. 转化生长因子β1对培养的瘢痕成纤维细胞增殖的调控作用 [J]. 中国组织化学与细胞化学杂志, 2006, 15(1): 3033.
22.	Wang R, Ghahary A, Shen Q, et al. Hypertrophic scar tissues and fibroblasts produce more transforming growth factorβ1 mRNA and protein than normal skin and cells [J]. Wound Repair Regen, 2000, 8(2): 128137.
23.	Kwak HJ, Park MJ, Cho H, et al. Transforming growth factorβ1 induces tissue inhibitor of metalloproteinase1 expression via activation of extracellular signalregulated kinase and Sp1 in human fibrosarcoma cells [J]. Mol Cancer Res, 2006, 4(3): 209220.
24.	Singh NN, Ramji DP. The role of transforming growth factorβ in atherosclerosis cytokine [J]. Growth Factor Rev, 2006, 17(06): 489499.
25.	Nedelec B, Ghahary A, Scott PG, et al. Control of wound contraction. Basic and clinical features [J]. Hand Clin, 2000, 16(2): 289302.
26.	Sumiyoshi K, Nakao A, Setoguchi Y, et al. Smads regulate collagen gel contraction by human dermal fibroblasts [J]. Br J Dermatol, 2003, 149(3): 464470.

1. Oga T, Matsuoka T, Yao C, et al. Prostaglandin F2α receptor signaling facilitates bleomycininduced pulmonary fibrosis independently of transforming growth factorβ [J]. Nat Med, 2009, 15: 14261430.
2. 耿智敏, 向国安, 韩庆, 等. 平滑肌肌动蛋白(SMA)在胆道愈合过程中的表达及意义 [J]. 肝胆外科杂志, 2000, 8(4): 312313.
3. 韩少山, 刘青光, 姚英民, 等. UbcH10在肝细胞癌中的表达及临床病理意义 [J]. 南方医科大学学报, 2011, 31(2): 280284.
4. Sváb J, Pesková M, Krska Z, et al. Prevention, diagnosis and treatment of iatrogennic lesions of biliary tract during laparoscopic cholecystectomy. Management of papila injury after invasive endoscopy. Part 1. Prevention and diagnosis of bile duct injuries [J]. Rozhl Chir, 2005, 84(4): 176181.
5. 黄志强. 胆管损伤: 肝胆外科永久的议题 [J]. 中华普通外科杂志, 2001, 16(6): 371373.
6. Geng ZM, Yao YM, Liu QG, et al. Mechanism of benign biliary stricture: a morphological and immunohistochemical study [J]. World J Gastroenterol, 2005, 11(2): 293295.
7. Prat F, Chapat O, Ducot B, et al. Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline [J]. Gut, 1998, 42(1): 7680.
8. Sohn TA, Yeo CJ, Cameron JL, et al. Do preoperative biliary stents increase postpancreaticoduodenectomy complications? [J]. J Gastrointest Surg, 2000, 4(3): 258267.
9. 耿智敏, 向国安, 韩庆, 等. 巨噬细胞及转化生长因子β1在肝外胆管损伤修复过程中的表达及其意义 [J]. 中华实验外科杂志, 2000, 17(6): 522523.
10. 耿智敏, 刘青光, 潘承恩, 等. 肌成纤维细胞在胆道愈合过程中的表达及意义 [J]. 中华实验外科杂志, 2001, 18(3): 205206.
11. 耿智敏, 徐军, 刘青光, 等. 良性胆管狭窄形成机制的研究 [J]. 消化外科, 2002, 1(5): 321323.
12. 耿智敏, 向国安, 韩庆, 等. 转化生长因子β1 在胆管愈合过程中的表达及意义 [J]. 中国普外基础与临床杂志, 2000, 7(6): 362363.
13. Sales KJ, Milne SA, Williams AR, et al. Expression, localization, and signaling of prostaglandin F2α receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogenactivated protein kinase signaling pathways [J]. J Clin Endocrinol Metab, 2004, 89(2): 986993.
14. Zaragoza DB, Wilson RR, Mitchell BF, et al. The interleukin 1βinduced expression of human prostaglandin F2α receptor messenger RNA in human myometrialderived ULTR cells requires the transcription factor, NFkappaB [J]. Biol Reprod, 2006, 75(5): 697704.
15. Olman MA. Beyond TGFβ: a prostaglandin promotes fibrosis [J]. Nat Med, 2009, 15(12): 13601361.
16. 梁君蓉, 王新, 吴开春, 等. COX2抑制剂对成纤维细胞的增殖和细胞外基质产生的影响 [J]. 第四军医大学学报, 2004, 25(9): 811814.
17. Jackson BA, Goldstein RH, Roy R, et al. Effects of transforming growth factor β and interleukin1β on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture [J]. Biochem Biophys Res Commun, 1993, 197(3): 14651474.
18. Luo J, Lang JA, Miller MW. Transforming growth factor β1 regulates the expression of cyclooxygenase in cultured cortical astrocytes and neurons [J]. J Neurochem, 1998, 71(2): 526534.
19. Fong CY, Pang L, Holland E, et al. TGFβ1 stimulates IL8 release, COX2 expression, and PGE2 release in human airway smooth muscle cells [J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(1): L201L207.
20. 张小文, 施国明, 邹浩, 等. 良性胆管狭窄瘢痕中CD68、TGFβ1、αSMA的表达 [J]. 中华肝胆外科杂志, 2007, 13(11): 750753.
21. 谢举临, 利天增, 祁少海, 等. 转化生长因子β1对培养的瘢痕成纤维细胞增殖的调控作用 [J]. 中国组织化学与细胞化学杂志, 2006, 15(1): 3033.
22. Wang R, Ghahary A, Shen Q, et al. Hypertrophic scar tissues and fibroblasts produce more transforming growth factorβ1 mRNA and protein than normal skin and cells [J]. Wound Repair Regen, 2000, 8(2): 128137.
23. Kwak HJ, Park MJ, Cho H, et al. Transforming growth factorβ1 induces tissue inhibitor of metalloproteinase1 expression via activation of extracellular signalregulated kinase and Sp1 in human fibrosarcoma cells [J]. Mol Cancer Res, 2006, 4(3): 209220.
24. Singh NN, Ramji DP. The role of transforming growth factorβ in atherosclerosis cytokine [J]. Growth Factor Rev, 2006, 17(06): 489499.
25. Nedelec B, Ghahary A, Scott PG, et al. Control of wound contraction. Basic and clinical features [J]. Hand Clin, 2000, 16(2): 289302.
26. Sumiyoshi K, Nakao A, Setoguchi Y, et al. Smads regulate collagen gel contraction by human dermal fibroblasts [J]. Br J Dermatol, 2003, 149(3): 464470.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of Prostaglandin F2α Receptor and Cyclooxygenase-2 in Tissue of Benign Bile Duct Scar and Their Significances

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