Role of Pancreatic Stellate Cells in Pancreatic Fibrosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHENG Zhenjiang , XIANG Guangming , LIU Xubao

Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Pancreatic stellate cells; Pancreatic fibrosis; Chronic pancreatitis; Treatment

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Objective To introduce the role of pancreatic stellate cells in pancreatic fibrosis and the progress in treatment of pancreatic fibrosis.
MethodsRelevant literatures were collected and reviewed.
Results Pancreatic stellate cells activation was closely related to pancreatic fibrosis. Inhibition of pancreatic stellate cells activation could provide a new approach in clinical treatment of chronic pancreatitis.
Conclusion Pancreatic stellate cells are the key to pancreatic fibrosis, which are becoming the target for antifibrosis of the pancreas and treatment of chronic pancreatitis.

Citation： ZHENG Zhenjiang ,XIANG Guangming,LIU Xubao. Role of Pancreatic Stellate Cells in Pancreatic Fibrosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(8): 876-879. doi: Copy

1.	Masamune A, Shimosegawa T. Signal transduction in pancreatic stellate cells [J]. J Gastroenterol, 2009; 44(4): 249260.
2.	Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture [J]. Gut, 1998; 43(1): 128133.
3.	Saotome T, Inoue H, Fujimiya M, et al. Morphological and immunocytochemical identification of periacinar fibroblastlike cells derived from human pancreatic acini [J]. Pancreas, 1997; 14(4): 373382.
4.	Haber PS, Keogh GW, Apte MV, et al. Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis [J]. Am J Pathol, 1999; 155(4): 10871095.
5.	Shimizu K. Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis [J]. J Gastroenterol, 2008; 43(11): 823832.
6.	Jaster R, Emmrich J. Crucial role of fibrogenesis in pancreatic diseases [J]. Best Pract Res Clin Gastroenterol, 2008; 22(1): 1729.
7.	Mews P, Phillips P, Fahmy R, et al. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis [J]. Gut, 2002; 50(4): 535541.
8.	Aoki H, Ohnishi H, Hama K, et al. Existence of autocrine loop between interleukin6 and transforming growth factorβ1 in activated rat pancreatic stellate cells [J]. J Cell Biochem, 2006; 99(1): 221228.
9.	Schneider E, SchmidKotsas A, Zhao J, et al. Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells [J]. Am J Physiol Cell Physiol, 2001; 281(2): C532C543.
10.	Yadav D, Whitcomb DC. The role of alcohol and smoking in pancreatitis [J]. Nat Rev Gastroenterol Hepatol, 2010; 7 (3): 131145.
11.	Ohnishi N, Miyata T, Ohnishi H, et al. Activin A is an autocrine activator of rat pancreatic stellate cells: potential role of follistatin for pancreatic fibrosis [J]. Gut, 2003; 52(10): 14871493.
12.	Philipps PA, Wu MJ, Kumar RK, et al. Cell migration: a novel aspect of pancreatic stellate cell biology [J]. Gut, 2003; 52(5): 677682.
13.	Leung PS. The physiology of a local reninangiotensin system in the pancreas [J]. J Physiol, 2007; 580(Pt1): 3137.
14.	Reinehr R, Zoller S, KlonowskiStumpe H, et al. Effects of Angiotensin II on rat pancreatic stellate cells [J]. Pancreas, 2004; 28(2): 129137.
15.	Owens DM, Keyse SM. Differential regulation of MAP kinase signalling by dualspecificity protein phosphatases [J]. Oncogene, 2007; 26(22): 32033213.
16.	Jaster R, Sparmann G, Emmrich J, et al. Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells [J]. Gut, 2002; 51(4): 579584.
17.	杨小艳, 郑勇. Smad7对TGFβ/SMAD的调节及其在肝纤维化中的作用 [J]. 临床肝胆胰杂志, 2007; 23(6): 467469.
18.	马松林, 赵秋, 龚勇, 等. 纤维化胰腺组织中TGFβ1、Smad3、Smad7的表达及意义 [J]. 世界华人消化杂志, 2007; 15(2): 185188.
19.	Dooley S, Hamzavi J, Breitkopf K, et al. Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J]. Gastroenterology, 2003; 125(1): 178191.
20.	McCarroll JA, Phillips PA, Kumar RK, et al. Pancreatic stellate cell migration: role of the phosphatidylinositol 3kinase (PI3kinase) pathway [J]. Biochem Pharmacol, 2004; 67(6): 12151225.
21.	Masamune A, Kikuta K, Satoh M, et al. Rho kinase inhibitors block activation of pancreatic stellate cells [J]. Br J Pharmacol, 2003; 140(7): 12921302.
22.	刘续宝. 慢性胰腺炎的诊断和治疗 [J]. 中国普外基础与临床杂志, 2007; 14(4): 385387.
23.	Rockey DC, Maher JJ, Jarnagin WR, et al. Inhibition of rat hepatic lipocyte activation in culture by IFNγ [J]. Hepatology, 1992; 16(3): 776784.
24.	Baumert JT, Sparmann G, Emmrich J, et al. Inhibitory effect of interferons on pancreatic stellate cell activation [J]. World J Gastroenterol, 2006; 12(6): 896901.
25.	Rane SG, Reddy EP. Janus kinases: components of multiple signaling pathways [J]. Oncogene, 2000; 19(49): 56625679.
26.	黄茜, 陈少夫, 郑宏. 干扰素α2b对胰腺纤维化大鼠Ⅲ型胶原和纤维连接蛋白表达的影响 [J]. 胰腺病学, 2007; 7(5): 326328.
27.	鲍华英, 陈荣华. 姜黄素的研究进展 [J]. 国际儿科学杂志, 2003; 30(5): 254256.
28.	Masamune A, Suzuki N, Kikuta K, et al. Curcumin blocks activation of pancreatic stellate cells [J]. J Cell Biochem, 2006; 97(5): 10801093.
29.	侯懿耕, 张园园, 贾洁, 等. 过氧化物酶体增殖物激活受体γ在肝星状细胞静止表型维持中的作用 [J]. 世界华人消化杂志, 2008; 16(33): 37653768.
30.	Van Westerloo DJ, Florquin S, deBoer AM, et al. Therapeutic effects of troglitazone in experimental chronic pancreatitis in mice [J]. Am J Pathol, 2005; 166(3): 721728.
31.	Shimuzu K, Shiratori K, Kobayashi M, et al. Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPAR γindependent mechanism [J]. Pancreas, 2004; 29(1): 6774.
32.	Tahmasebi M, Puddefoot JR, Inwang ER, et al. The tissue reninangiotensin system in human pancreas [J]. J Endocrinol, 1999; 161(2): 317322.
33.	Kuno A, Yamada T, Masuda K, et al. Angiotensinconverting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats [J]. Gastroenterology, 2003; 124(4): 10101019.
34.	张汝玲, 刘文滨, 王兴鹏, 等.Ⅰ型血管紧张素Ⅱ受体拮抗剂对胰腺星状细胞的影响 [J]. 中华消化杂志, 2006; 26(9): 598601.
35.	Nathan JD, Romac J, Peng RY, et al. Protection against chronic pancreatitis and pancreatic fibrosis in mice over expressing pancreatic secretory trypsin inhibitor [J]. Pancreas, 2010; 39(1): e24e30.
36.	Su SB, Motoo Y, Iovanna JL, et al. Effect of camostat mesilate on the expression of PancreaticAssociated Protein (PAP), p8 and cytokines in rat spontaneous chronic pancreatitis [J]. Pancreas, 2001; 23(2): 134140.
37.	McCarroll JA, Phillips PA, Santucci N, et al. Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis [J]. Gut, 2006; 55(1): 7989.
38.	Masamune A, Satoh M, Kikuta K, et al. Endothelin1 stimulates contraction and migration of rat pancreatic stellate cells [J]. World J Gastroenterol, 2005; 11(39): 61446151.
39.	罗璐, 于锋, 戴德哉. 内皮素受体拮抗剂波生坦与其他药物的相互作用 [J]. 药学进展, 2007; 31(10): 452457.
40.	Fitzner B, Brock P, Holzhüter SA, et al. Synergistic growth inhibitory effects of the dual endothelin1 receptor antagonist bosentan on pancreatic stellate and cancer cells [J]. Dig Dis Sci, 2009; 54(2): 309320.

1. Masamune A, Shimosegawa T. Signal transduction in pancreatic stellate cells [J]. J Gastroenterol, 2009; 44(4): 249260.
2. Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture [J]. Gut, 1998; 43(1): 128133.
3. Saotome T, Inoue H, Fujimiya M, et al. Morphological and immunocytochemical identification of periacinar fibroblastlike cells derived from human pancreatic acini [J]. Pancreas, 1997; 14(4): 373382.
4. Haber PS, Keogh GW, Apte MV, et al. Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis [J]. Am J Pathol, 1999; 155(4): 10871095.
5. Shimizu K. Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis [J]. J Gastroenterol, 2008; 43(11): 823832.
6. Jaster R, Emmrich J. Crucial role of fibrogenesis in pancreatic diseases [J]. Best Pract Res Clin Gastroenterol, 2008; 22(1): 1729.
7. Mews P, Phillips P, Fahmy R, et al. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis [J]. Gut, 2002; 50(4): 535541.
8. Aoki H, Ohnishi H, Hama K, et al. Existence of autocrine loop between interleukin6 and transforming growth factorβ1 in activated rat pancreatic stellate cells [J]. J Cell Biochem, 2006; 99(1): 221228.
9. Schneider E, SchmidKotsas A, Zhao J, et al. Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells [J]. Am J Physiol Cell Physiol, 2001; 281(2): C532C543.
10. Yadav D, Whitcomb DC. The role of alcohol and smoking in pancreatitis [J]. Nat Rev Gastroenterol Hepatol, 2010; 7 (3): 131145.
11. Ohnishi N, Miyata T, Ohnishi H, et al. Activin A is an autocrine activator of rat pancreatic stellate cells: potential role of follistatin for pancreatic fibrosis [J]. Gut, 2003; 52(10): 14871493.
12. Philipps PA, Wu MJ, Kumar RK, et al. Cell migration: a novel aspect of pancreatic stellate cell biology [J]. Gut, 2003; 52(5): 677682.
13. Leung PS. The physiology of a local reninangiotensin system in the pancreas [J]. J Physiol, 2007; 580(Pt1): 3137.
14. Reinehr R, Zoller S, KlonowskiStumpe H, et al. Effects of Angiotensin II on rat pancreatic stellate cells [J]. Pancreas, 2004; 28(2): 129137.
15. Owens DM, Keyse SM. Differential regulation of MAP kinase signalling by dualspecificity protein phosphatases [J]. Oncogene, 2007; 26(22): 32033213.
16. Jaster R, Sparmann G, Emmrich J, et al. Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells [J]. Gut, 2002; 51(4): 579584.
17. 杨小艳, 郑勇. Smad7对TGFβ/SMAD的调节及其在肝纤维化中的作用 [J]. 临床肝胆胰杂志, 2007; 23(6): 467469.
18. 马松林, 赵秋, 龚勇, 等. 纤维化胰腺组织中TGFβ1、Smad3、Smad7的表达及意义 [J]. 世界华人消化杂志, 2007; 15(2): 185188.
19. Dooley S, Hamzavi J, Breitkopf K, et al. Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J]. Gastroenterology, 2003; 125(1): 178191.
20. McCarroll JA, Phillips PA, Kumar RK, et al. Pancreatic stellate cell migration: role of the phosphatidylinositol 3kinase (PI3kinase) pathway [J]. Biochem Pharmacol, 2004; 67(6): 12151225.
21. Masamune A, Kikuta K, Satoh M, et al. Rho kinase inhibitors block activation of pancreatic stellate cells [J]. Br J Pharmacol, 2003; 140(7): 12921302.
22. 刘续宝. 慢性胰腺炎的诊断和治疗 [J]. 中国普外基础与临床杂志, 2007; 14(4): 385387.
23. Rockey DC, Maher JJ, Jarnagin WR, et al. Inhibition of rat hepatic lipocyte activation in culture by IFNγ [J]. Hepatology, 1992; 16(3): 776784.
24. Baumert JT, Sparmann G, Emmrich J, et al. Inhibitory effect of interferons on pancreatic stellate cell activation [J]. World J Gastroenterol, 2006; 12(6): 896901.
25. Rane SG, Reddy EP. Janus kinases: components of multiple signaling pathways [J]. Oncogene, 2000; 19(49): 56625679.
26. 黄茜, 陈少夫, 郑宏. 干扰素α2b对胰腺纤维化大鼠Ⅲ型胶原和纤维连接蛋白表达的影响 [J]. 胰腺病学, 2007; 7(5): 326328.
27. 鲍华英, 陈荣华. 姜黄素的研究进展 [J]. 国际儿科学杂志, 2003; 30(5): 254256.
28. Masamune A, Suzuki N, Kikuta K, et al. Curcumin blocks activation of pancreatic stellate cells [J]. J Cell Biochem, 2006; 97(5): 10801093.
29. 侯懿耕, 张园园, 贾洁, 等. 过氧化物酶体增殖物激活受体γ在肝星状细胞静止表型维持中的作用 [J]. 世界华人消化杂志, 2008; 16(33): 37653768.
30. Van Westerloo DJ, Florquin S, deBoer AM, et al. Therapeutic effects of troglitazone in experimental chronic pancreatitis in mice [J]. Am J Pathol, 2005; 166(3): 721728.
31. Shimuzu K, Shiratori K, Kobayashi M, et al. Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPAR γindependent mechanism [J]. Pancreas, 2004; 29(1): 6774.
32. Tahmasebi M, Puddefoot JR, Inwang ER, et al. The tissue reninangiotensin system in human pancreas [J]. J Endocrinol, 1999; 161(2): 317322.
33. Kuno A, Yamada T, Masuda K, et al. Angiotensinconverting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats [J]. Gastroenterology, 2003; 124(4): 10101019.
34. 张汝玲, 刘文滨, 王兴鹏, 等.Ⅰ型血管紧张素Ⅱ受体拮抗剂对胰腺星状细胞的影响 [J]. 中华消化杂志, 2006; 26(9): 598601.
35. Nathan JD, Romac J, Peng RY, et al. Protection against chronic pancreatitis and pancreatic fibrosis in mice over expressing pancreatic secretory trypsin inhibitor [J]. Pancreas, 2010; 39(1): e24e30.
36. Su SB, Motoo Y, Iovanna JL, et al. Effect of camostat mesilate on the expression of PancreaticAssociated Protein (PAP), p8 and cytokines in rat spontaneous chronic pancreatitis [J]. Pancreas, 2001; 23(2): 134140.
37. McCarroll JA, Phillips PA, Santucci N, et al. Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis [J]. Gut, 2006; 55(1): 7989.
38. Masamune A, Satoh M, Kikuta K, et al. Endothelin1 stimulates contraction and migration of rat pancreatic stellate cells [J]. World J Gastroenterol, 2005; 11(39): 61446151.
39. 罗璐, 于锋, 戴德哉. 内皮素受体拮抗剂波生坦与其他药物的相互作用 [J]. 药学进展, 2007; 31(10): 452457.
40. Fitzner B, Brock P, Holzhüter SA, et al. Synergistic growth inhibitory effects of the dual endothelin1 receptor antagonist bosentan on pancreatic stellate and cancer cells [J]. Dig Dis Sci, 2009; 54(2): 309320.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Role of Pancreatic Stellate Cells in Pancreatic Fibrosis

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