Initial Study on Effect of Peroxisome Proliferator-Activated ReceptorγAgonist on Bile Duct Fibrosis Induced by Transforming Growth Factor-β1_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 JINYan-wen , YEHui , XIONGXian-ze , LIFu-yu , ZHOURong-xing ,  ChengNan-sheng

Department of Biliary Surgery, West China Hospital, Sichuan University. Chengdu 610041, Sichuan Province, China;

Corresponding?author：

ChengNan-sheng, Email: chengnansheng2014@126.com

Keywords：

Peroxisome proliferator-activated receptorγ; Transforming growth factor-β1; Fibroblast; Bile duct fibrosis

DOI：

10.7507/1007-9424.20160208

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of peroxisome proliferator-activated receptorγ(PPARγ) agonist on bile duct fibrosis induced by transforming growth factor-β1 (TGF-β1). Methods Primary cultures of bile duct fibroblast were treated with different concentrations of pioglitazone (PGZ) or 15-deoxy-Δ^{12, 14}-prostaglandin J₂ (15d-PGJ₂) and then treated with TGF-β1. The mRNA levels of collagenⅠ(COLⅠ)、fibronectin (FN)、α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) were determined by RT-PCR. Results PGZ and 15-d-PGJ₂ could down regulated the mRNA levels of COLⅠ, FN, α-SMA and CTGF induced by TGF-β1 (3 ng/mL). The same concentration of 15d-PGJ₂ was a more potent inhibitor ofα-SMA and less potent inhibitor of COLⅠthan PGZ. But PGZ had the same effect as 15d-PGJ₂ on CTGF. Conclusion PPARγagonist can prevent fibrosis induced by TGF-β1.

Citation： JINYan-wen, YEHui, XIONGXian-ze, LIFu-yu, ZHOURong-xing, ChengNan-sheng. Initial Study on Effect of Peroxisome Proliferator-Activated ReceptorγAgonist on Bile Duct Fibrosis Induced by Transforming Growth Factor-β1. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(7): 790-793. doi: 10.7507/1007-9424.20160208 Copy

1.	Fukui T, Nakayama S, Shimatani M, et al. Endoscopic biliary plastic stenting and successful intentional stent retrieval in a benign biliary stricture with mural spherical calcification and porcelain gallbladder. Intern Med, 2009, 48(10): 809-813.
2.	李富宇, 李寧, 蔣力生, 等.淺談慢性增生性膽管炎在肝內膽管結石防治中的意義.中華肝膽外科雜志, 2008, 14(4): 225-228.
3.	胡冰.規范膽管良性狹窄的內鏡治療.中華消化內鏡雜志, 2009, 26(5): 231-233.
4.	Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol, 2008, 214(2): 199-210.
5.	Wrana JL, Attisano L, Cárcamo J, et al. TGF beta signals through a heteromeric protein kinase receptor complex. Cell, 1992, 71(6): 1003-1014.
6.	Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003, 113(6): 685-700.
7.	Chawla A, Repa JJ, Evans RM, et al. Nuclear receptors and lipid physiology: opening the X-files. Science, 2001, 294(5548): 1866-1870.
8.	Sonoda J, Pei L, Evans RM. Nuclear receptors: decoding metabolic disease. Febs Lett, 2008, 582(1): 2-9.
9.	Zhao CY, Chen W, Yang L, et al. PPAR gamma agonists prevent TGFβ1 Smad3-signaling in human hepatic stellate cells. Biochem Biophys Res Commun, 2006, 350(2): 385-391.
10.	Zou R, Xu G, Liu XC, et al. PPARy agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin, 2010, 31(1): 43-50.
11.	司徒鎮強, 吳軍正.細胞培養.第2版.西安:世界圖書出版公司, 1996: 69-71.
12.	Chandra V, Huang P, Hamuro Y, et al. Structure of the intact PPAR-γ-RXR-nuclear receptor complex on DNA. Nature, 2008, 456(7220): 350-356.
13.	Ferguson HE, Kulkarni A, Lehmann GM, et al. Electrophilic peroxisome proliferator-activated receptor-gamma ligands have potent antifibrotic effects in human lung fibroblasts. Am J Resp Cell Mol, 2009, 41(6): 722-730.
14.	Ghosh AK, Bhattacharyya S, Lakos G, et al. Disruption of transfor-ming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma. Arthritis Rheum, 2004, 50(4): 1305-1318.
15.	Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPARγ). J Biol Chem, 1995, 270(22): 12953-12956.
16.	Straus DS, Pascual G, Li M, et al.15-deoxy-delta 12, 14-prostaglandin J₂ inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA, 2000, 97(9): 4844-4849.
17.	Delerive P, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol, 2001, 169(3): 453-459.
18.	Burgess HA, Daugherty LE, Thatcher TH, et al. PPARγagonists inhibit TGF-βinduced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol-Lung C, 2005, 288(6): L1146-L1153.
19.	Shi-wen X, Pennington D, Holmes A, et al. Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis. Exp Cell Res, 2000, 259(1): 213-224.
20.	Shimo T, Nakanishi T, Nishida T, et al. Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo. J Biochem, 1999, 126(1): 137-145.
21.	Grotendorst GR. Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev, 1997, 8(3): 171-179.
22.	Mori T, Kawara S, Shinozaki M, et al. Role and interaction of conne-ctive tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol, 1999, 181(1): 153-159.
23.	Shi-wen X, Stanton LA, Kennedy L, et al. CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblasts. J Biol Chem, 2006, 281(16): 10715-10726.
24.	Liu S, Shi-wen X, Abraham DJ, et al. CCN2 is required for bleomycin-induced skin fibrosis in mice. Arthritis Rheum, 2011, 63(1): 239-246.
25.	Ponticos M, Holmes AM, Shi-wen X, et al. Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcrip-tional activation of type I collagen. Arthritis Rheum, 2009, 60(7): 2142-2155.

1. Fukui T, Nakayama S, Shimatani M, et al. Endoscopic biliary plastic stenting and successful intentional stent retrieval in a benign biliary stricture with mural spherical calcification and porcelain gallbladder. Intern Med, 2009, 48(10): 809-813.
2. 李富宇, 李寧, 蔣力生, 等.淺談慢性增生性膽管炎在肝內膽管結石防治中的意義.中華肝膽外科雜志, 2008, 14(4): 225-228.
3. 胡冰.規范膽管良性狹窄的內鏡治療.中華消化內鏡雜志, 2009, 26(5): 231-233.
4. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol, 2008, 214(2): 199-210.
5. Wrana JL, Attisano L, Cárcamo J, et al. TGF beta signals through a heteromeric protein kinase receptor complex. Cell, 1992, 71(6): 1003-1014.
6. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003, 113(6): 685-700.
7. Chawla A, Repa JJ, Evans RM, et al. Nuclear receptors and lipid physiology: opening the X-files. Science, 2001, 294(5548): 1866-1870.
8. Sonoda J, Pei L, Evans RM. Nuclear receptors: decoding metabolic disease. Febs Lett, 2008, 582(1): 2-9.
9. Zhao CY, Chen W, Yang L, et al. PPAR gamma agonists prevent TGFβ1 Smad3-signaling in human hepatic stellate cells. Biochem Biophys Res Commun, 2006, 350(2): 385-391.
10. Zou R, Xu G, Liu XC, et al. PPARy agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin, 2010, 31(1): 43-50.
11. 司徒鎮強, 吳軍正.細胞培養.第2版.西安:世界圖書出版公司, 1996: 69-71.
12. Chandra V, Huang P, Hamuro Y, et al. Structure of the intact PPAR-γ-RXR-nuclear receptor complex on DNA. Nature, 2008, 456(7220): 350-356.
13. Ferguson HE, Kulkarni A, Lehmann GM, et al. Electrophilic peroxisome proliferator-activated receptor-gamma ligands have potent antifibrotic effects in human lung fibroblasts. Am J Resp Cell Mol, 2009, 41(6): 722-730.
14. Ghosh AK, Bhattacharyya S, Lakos G, et al. Disruption of transfor-ming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma. Arthritis Rheum, 2004, 50(4): 1305-1318.
15. Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPARγ). J Biol Chem, 1995, 270(22): 12953-12956.
16. Straus DS, Pascual G, Li M, et al.15-deoxy-delta 12, 14-prostaglandin J₂ inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA, 2000, 97(9): 4844-4849.
17. Delerive P, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol, 2001, 169(3): 453-459.
18. Burgess HA, Daugherty LE, Thatcher TH, et al. PPARγagonists inhibit TGF-βinduced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol-Lung C, 2005, 288(6): L1146-L1153.
19. Shi-wen X, Pennington D, Holmes A, et al. Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis. Exp Cell Res, 2000, 259(1): 213-224.
20. Shimo T, Nakanishi T, Nishida T, et al. Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo. J Biochem, 1999, 126(1): 137-145.
21. Grotendorst GR. Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev, 1997, 8(3): 171-179.
22. Mori T, Kawara S, Shinozaki M, et al. Role and interaction of conne-ctive tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol, 1999, 181(1): 153-159.
23. Shi-wen X, Stanton LA, Kennedy L, et al. CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblasts. J Biol Chem, 2006, 281(16): 10715-10726.
24. Liu S, Shi-wen X, Abraham DJ, et al. CCN2 is required for bleomycin-induced skin fibrosis in mice. Arthritis Rheum, 2011, 63(1): 239-246.
25. Ponticos M, Holmes AM, Shi-wen X, et al. Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcrip-tional activation of type I collagen. Arthritis Rheum, 2009, 60(7): 2142-2155.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Initial Study on Effect of Peroxisome Proliferator-Activated ReceptorγAgonist on Bile Duct Fibrosis Induced by Transforming Growth Factor-β1

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