vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2018-15-4-455-464vestim-460Research ArticleОБЗОРЫREVIEWSРоль звездчатых клеток в морфогенезе хронического панкреатитаRole of stellate cells in the morphogenesis of chronic pancreatitisМожейкоЛ. А.MozhejkoL. A.

канд. мед. наук, доцент

Ph. D. (Med.), Assistant Professor

mozhejko-hist@yandex.ruГродненский государственный медицинский университет, ГродноGrodno State Medical University, Grodno201814012019154455464Copyright © Можейко Л.А., 20192019Можейко Л.А.Mozhejko L.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/460

В настоящем обзоре представлен анализ литературных сведений о роли панкреатических звездчатых клеток (ПЗК) в патогенезе фиброза, являющегося основным гистологическим признаком хронического алкогольного панкреатита. Показано, что этанол и токсичные продукты его обмена могут воздействовать на ПЗК прямым и непрямым путем, способствуя их трансформации из покоящегося в активное состояние. В процессе развития патологического процесса ПЗК взаимодействуют с паренхиматозными и иммунными клетками поджелудочной железы посредством цитокинов и ростовых факторов. В активированных ПЗК увеличиваются пролиферативная и миграционная активность, а также синтез белков экстрацеллюлярного матрикса (ЭЦМ). Постоянная активация ПЗК в течение заболевания способствует поддержанию воспаления, накоплению избыточных количеств белков ЭЦМ и развитию панкреатического фиброза.

 

This review presents an analysis of the literature on the role of pancreatic stellate cells (PSCs) in the pathogenesis of fibrosis, a predominant histological feature of chronic alcoholic pancreatitis. It is shown that ethanol and toxic products of its metabolism can affect PSCs directly and indirectly, facilitating their transformation from a quiescent to an activated state. During the pathological process, PSCs interact with parenchymal and immune cells of the pancreas through cytokines and growth factors. In activated PSCs, the proliferative and migratory activity, as well as the synthesis of extracellular matrix (ECM) proteins increases. A continuous activation of PSCs during the disease promotes the maintenance of inflammation, the deposition of excessive amounts of ECM proteins and the development of pancreatic fibrosis.

хронический панкреатитзвездчатые панкреатические клеткипанкреатический фиброзchronic pancreatitisstellate pancreatic cellspancreatic fibrosisReferencesРевтович, М. Ю. Хронический панкреатит: некоторые аспекты проблемы / М. Ю. Ревтович, С. И. Леонович // Мед. журн. – 2006. – № 4. – С. 14–16.Revtovich M. Yu., Leonovich S. I. Chronic pancreatitis: some aspects of the problem. Meditsinskii zhurnal [Medical journal], 2006, no. 4, pp. 14–16 (in Russian).Сiренко, О. Ю. Панкреатичнi зiрчастi клiтини як морфологiчна основа розвитку фiброзу пiдшлункової залози / О. Ю. Сiренко // Морфологiя. – 2010. – Т. 4, № 1. – С. 5–12.Sirenko O. Yu. Pancreatic stellate cells as a morphological basis for the development of pancreatic fibrosis. Morfologiya [Morphology], 2010, vol. 4, no. 1, pp. 5–12 (in Ukrainian).Взаимосвязь фиброза и гипоксии поджелудочной железы в патогенезе хронического панкреатита / А. В. Воробей [и др.] // Укр. журн. хирургии. – 2017. – № 2 (33). – С. 10–20.Vorobei A. V., Shuleiko A. Ch., Vladimirskaya T. E., Shved I. A., Vizhinis E. I., Orlovskii Yu. N., Makki M. Yu. Interrelation of fibrosis and pancreatic hypoxia in pathogenesis of chronic pancreatitis. Ukrainskii zhurnal khirurgii = Ukrainian journal of surgery, 2017, no. 2 (33), pp. 10–20 (in Ukrainian).Apte, M. Pancreatic stellate cell: physiologic role, role in fibrosis and cancer / M. Apte, R. C. Pirola, J. S. Wilson // Curr. Opin. Gastroenterol. – 2015. – Vol. 31, N 5. – P. 416–423. https://doi.org/10.1097/mog.0000000000000196Apte M., Pirola R. C., Wilson J. S. Pancreatic stellate cell: physiologic role, role in fibrosis and cancer. Current Opinion in Gastroenterology, 2015, vol. 31, no. 5, pp. 416–423. https://doi.org/10.1097/mog.0000000000000196Pancreatic stellate cell: Pandora’s box for pancreatic disease biology / R. R. Bynigeri [et al.] // World J. Gastroenterol. – 2017. – Vol. 23, N 3. – P. 382–405. https://doi.org/10.3748/wjg.v23.i3.382Bynigeri R. R., Jakkampudi A., Jangala R., Subramanyam C., Sasikala M., Venkat G. Rao, Nageshwar D. R, Talukdar R. Pancreatic stellate cell: Pandora’s box for pancreatic disease biology. World Journal of Gastroenterology, 2017, vol. 23, no. 3, pp. 382–405. https://doi.org/10.3748/wjg.v23.i3.382Mössner, J. Epidemiology of chronic pancreatitis / J. Mössner // Standards in pancreatic surgery / eds. : H. G. Beger, M. Büchler, P. Malfertheiner. – Berlin, 1993. – P. 263–271.Mössner J. Epidemiology of chronic pancreatitis. Standards in pancreatic surgery. Berlin, Springer, 1993, pp. 263–271.Pezzilli, R. Pancreatic stellate cells and chronic alcoholic pancreatitis // JOP. J. Pancreas. – 2007. – Vol. 8, N 2. – P. 254–257.Pezzilli R. Pancreatic stellate cells and chronic alcoholic pancreatitis. JOP. Journal of Pancreas, 2007, vol. 8, no. 2, pp. 254–257.Можейко, Л. А. Панкреатические звездчатые клетки: структура и функция. Ч. 1. Морфофункциональная характеристика панкреатических звездчатых клеток в физиологических условиях / Л. А. Можейко // Гепатология и гастроэнтерология. – 2018. – № 1. – С. 21–25.Mozheyko L. A. Рancreatic stellate cells: structure and function. Рt. 1. Morphofunctional characteristics of pancreatic stellate cells under physiological conditions. Gepatologiya i gastroenterologiya [Hepatology and Gastroenterology], 2018, no. 1, pp. 21–25 (in Russian).Identification, culture, and characterization of pancreatic stellate cells in rats and humans / M. G. Bachem [et al.] // Gastroenterology. – 1998. – Vol. 115, N 2. – P. 421–432. https://doi.org/10.1016/s0016-5085(98)70209-4Bachem M. G., Schneider E., Groß H., Weidenbach H., Schmid R. M., Menke A., Siech M., Beger H., Grünert A., Adler G. Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology, 1998, vol. 115, no. 2, pp. 421–432. https://doi.org/10.1016/s0016-5085(98)70209-4Apte, M. V. Dangerous liaisons: pancreatic stellate cells and pancreatic cancer cells / M. V. Apte, J. S. Wilson // J. Gastroenterol. Hepatol. – 2012. – Vol. 27, suppl. 2. – P. 69–74. https://doi.org/10.1111/j.1440-1746.2011.07000.xApte M. V., Wilson J. S. Dangerous liaisons: pancreatic stellate cells and pancreatic cancer cells. Journal of Gastroenterology and Hepatology, 2012, vol. 27, suppl. 2, pp. 69–74. https://doi.org/10.1111/j.1440-1746.2011.07000.xRat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover / P. A. Phillips [et al.] // Gut. – 2003. – Vol. 52, N 2. – P. 275–282. https://doi.org/10.1136/gut.52.2.275Phillips P. A., McCarroll J. A., Park S., Wu M.-J., Korsten M., Pirola R., Wilson J. S., Apte M. V. Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut, 2003, vol. 52, no. 2, pp. 275–282. https://doi.org/10.1136/gut.52.2.275Ferdek, P. E. Biology of pancreatic stellate cells – more than just pancreatic cancer / P. E. Ferdek, M. A. Jakubowska // Eur. J. Physiol. – 2017. – Vol. 469, N 9. – P. 1039–1050. https://doi.org/10.1007/s00424-017-1968-0Ferdek P. E., Jakubowska M. A. Biology of pancreatic stellate cells – more than just pancreatic cancer. European Journal of Physiology, 2017, vol. 469, no. 9, pp. 1039–1050. https://doi.org/10.1007/s00424-017-1968-0Wilson, J. S. Role of alcohol metabolism in alcoholic pancreatitis / J. S. Wilson, M. V. Apte // Pancreas. – 2003. – Vol. 27, N 4. – P. 311–315. https://doi.org/10.1097/00006676-200311000-00007Wilson J. S., Apte M. V. Role of alcohol metabolism in alcoholic pancreatitis. Pancreas, 2003, vol. 27, no. 4, pp. 311–315. https://doi.org/10.1097/00006676-200311000-00007Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells / M. V. Apte [et al.] // Gastroenterology. – 2000. – Vol. 118, N 4. – P. 780–794. https://doi.org/10.1016/s0016-5085(00)70148-xApte M. V., Phillips P. A., Fahmy R. G., Darby S. J., Rodgers S. C., McCaughan G. W., Korsten M. A., Pirola R. C., Naidoo D., Wilson J. S. Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells. Gastroenterology, 2000, vol. 118, no. 4, pp. 780–794. https://doi.org/10.1016/s0016-5085(00)70148-xApte, M. V. Battle-scarred pancreas: role of alcohol and pancreatic stellate cells in pancreatic fibrosis / M. V. Apte, R. C. Pirola, J. S. Wilson // J. Gastroenterol. Hepatol. – 2006. – Vol. 21, suppl. 3. – P. S97–S101. https://doi.org/10.1111/ j.1440-1746.2006.04587.xApte M. V., Pirola R. C., Wilson J. S. Battle-scarred pancreas: role of alcohol and pancreatic stellate cells in pancreatic fibrosis. Journal of Gastroenterology and Hepatology, 2006, vol. 21, suppl. 3, pp. S97–S101. https://doi.org/10.1111/ j.1440-1746.2006.04587.xEthanol augments PDGF-induced NADPH oxidase activity and proliferation in rat pancreatic stellate cells / R. Hu [et al.] // Pancreatology. – 2007. – Vol. 7, N 4. – P. 332–340. https://doi.org/10.1159/000105499Hu R., Wang Y.-L., Edderkaoui M., Lugea A., Apte M. V., Pandol S. J. Ethanol augments PDGF-induced NADPH oxidase activity and proliferation in rat pancreatic stellate cells. Pancreatology, 2007, vol. 7, no. 4, pp. 332–340. https://doi.org/10.1159/000105499Alcohol withdrawal promotes regression of pancreatic fibrosis via induction of Pancreatic Stellate Cell (PSC) apoptosis / A. Vonlaufen [et al.] // Gastroenterology. – 2011. – Vol. 136, N 5, suppl. 1. – P. A-589–A-590. https://doi.org/10.1016/S0016-5085(09)62716-5Vonlaufen A., Phillips P., Xu Zh., Zhang X., Yang L., Pirola R., Wilson J. S., Apte M. V. Alcohol withdrawal promotes regression of pancreatic fibrosis via induction of Pancreatic Stellate Cell (PSC) apoptosis. Gastroenterology, 2011, vol. 136, no. 5, suppl. 1, pp. A-589–A-590. https://doi.org/10.1016/S0016-5085(09)62716-5Reed, A. M. Animal models of chronic pancreatitis [Electronic resource] / A. M. Reed, F. S. Gorelick // Pancreapedia: Exocrine Pancreas Knowledge Base. – Mode of access : https://www.pancreapedia.org/reviews/animal-models-of-chronicpancreatitis. – Date of access : 20.09.2018.Reed A. M., Gorelick F. S. Animal models of chronic pancreatitis. Pancreapedia: Exocrine Pancreas Knowledge Base. Available at: https://www.pancreapedia.org/reviews/animal-models-of-chronic-pancreatitis (accessed 20.09.2018).Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis. / X. Zhan [et al.] // Am. J. Physiol. Gastrointest. Liver Physiol. – 2016. – Vol. 311, N 3. – P. G343–G355. https://doi.org/10.1152/ajpgi.00372.2015Zhan X., Wang F., Bi Y., Ji B. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2016, vol. 311, no. 3, pp. G343–G355. https://doi.org/10.1152/ajpgi.00372.2015Туманский, В. А. Тяжелый фиброз поджелудочной железы при хроническом панкреатите: основные патоморфологические составляющие, иммунофенотип фиброгенных клеток и коллагена / В. А. Туманский, И. С. Коваленко // Патологiя. – 2013. – № 1 (27). – С. 27–30.Tumanskii V. A., Kovalenko I. S. Severe fibrosis of the pancreas in chronic pancreatitis: main pathological components, immunophenotype of fibrogenic cells and collagen. Patologiya [Patology], 2013, no. 1 (27), pp. 27–30 (in Ukrainian).Hu, W. Simultane ous character ization of pancreatic stellate cells and other pancreatic components within three dimensional tissue environment during chronic pancreatitis. / W. Hu, L. Fu // J. Biomed. Optics. – 2013. – Vol. 18, N 5. – P. 056002. https://doi.org/10.1117/1.jbo.18.5.056002Wenyan Hu, Ling Fu. Simultane ous character ization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis. Journal of Biomedical Optics, 2013, vol. 18, no. 5, pp. 056002. https://doi.org/10.1117/1.jbo.18.5.056002Pancreas – pathological practice and research / ed. K. Suda. – Tokyo : Karger, 2007. – 318 p.Suda K. (ed.). Pancreas – pathological practice and research. Tokyo, Karger, 2007. 318 p.Bone marrow-derived pancreatic stellate cells in rats / G. Sparmann [et al.] // Cell Res. – 2010. – Vol. 20, N 3. – P. 288–298. https://doi.org/10.1038/cr.2010.10Sparmann G., Kruse M.-L., Hofmeister-Mielke N., Koczan D., Jaster R., Liebe S., Wolff D., Emmrich J. Bone marrowderived pancreatic stellate cells in rats. Cell Research, 2010, vol. 20, no. 3, pp. 288–298. https://doi.org/10.1038/cr.2010.10Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: angiogenesis in chronic pancreatitis and in pancreatic cancer / R. Kuehn [et al.] // Pancreas. – 1999. – Vol. 18, N 1. – P. 96–103. https://doi.org/10.1097/00006676-199901000-00012Kuehn R., Lelkes P. I., Bloechle C., Niendorf A., Izbicki J. R. Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: angiogenesis in chronic pancreatitis and in pancreatic cancer. Pancreas, 1999, vol. 18, no. 1, pp. 96–103. https://doi.org/10.1097/00006676-199901000-00012Mathematical model of chronic pancreatitis / W. Hao [et al.] // PNAS. – 2017. – Vol. 114, N 19. – P. 5011–5016. https://doi.org/10.1073/pnas.1620264114Hao W., Komar H. M., Hart P. A., Conwell D. L., Lesinski G. B., Friedman A. Mathematical model of chronic pancreatitis. Proceeding of the National Academy of Sciences, 2017, vol. 114, no. 19, рр. 5011–5016. https://doi.org/10.1073/ pnas.1620264114The pancreatic stellate cell: a star on the rise in pancreatic diseases / M. B. Omary [et al.] // J. Clin. Invest. – 2007. – Vol. 117, N 1. – P. 50–59. https://doi.org/10.1172/jci30082Omary M. B., Lugea A., Lowe A. W., Pandol S. J. The pancreatic stellate cell: a star on the rise in pancreatic diseases. Journal of Clinical Investigate, 2007, vol. 117, no. 1, рр. 50–59. https://doi.org/10.1172/jci30082Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis / P. Mews [et al.] // Gut. – 2002. – Vol. 50, N 4. – P. 535–541. https://doi.org/10.1136/gut.50.4.535Mews P., Phillips P., Fahmy R., Korsten M., Pirola R., Wilson J., Apte M. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis. Gut, 2002, vol. 50, no. 4, рр. 535–541. https://doi.org/10.1136/ gut.50.4.535Marra, F. Renaming cytokines: MCP-1, major chemokine in pancreatitis / F. Marra // Gut. – 2005. – Vol. 54, N 12. – P. 1679–1681. https://doi.org/10.1136/gut.2005.068593Marra F. Renaming cytokines: MCP-1, major chemokine in pancreatitis. Gut, 2005, vol. 54, no. 12, рр. 1679–1681. https://doi.org/10.1136/gut.2005.068593Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis / J. Xue [et al.] // Nat. Commun. – 2015. – Vol. 6, N 1. – P. 7158–7165. https://doi.org/10.1038/ncomms8158Xue J., Sharma V., Hsieh M. H., Chawla A., Murali R., Pandol S. J., Habtezion A. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis. Nature Communications, 2015, vol. 6, no. 1. https://doi.org/10.1038/ ncomms8158Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis / P. S. Haber [et al.] // Am. J. Pathol. – 1999. – Vol. 155, N 4. – P. 1087–1095. https://doi.org/10.1016/s0002-9440(10)65211-xHaber P. S., Keogh G. W., Apte M. V., Moran C. S., Stewart N. L., Crawford D. H. G., Pirola R. C., McCaughan G. W., Ramm G. A., Wilson J. S. Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. American Journal of Pathology, 1999, vol. 155, no. 4, рр. 1087–1095. https://doi.org/10.1016/s0002-9440(10)65211-xLigands of peroxisome proliferator-activated receptor-gamma block activation of pancreatic stellate cells / A. Masamune [et al.] // J. Biol. Chem. – 2001. – Vol. 277, N 1. – P. 141–147. https://doi.org/10.1074/jbc.m107582200Masamune A., Kikuta K., Satoh M., Sakai Y., Satoh A., Shimosegawa T. Ligands of peroxisome proliferator-activated receptor-gamma block activation of pancreatic stellate cells. Journal of Biological Chemistry, 2001, vol. 277, no. 1, рр. 141–147. https://doi.org/10.1074/jbc.m107582200Proteome variations in pancreatic stellate cells upon stimulation with proinflammatory factors / A. J. Marzoq [et al.] // J. Biol. Chem. – 2013. – Vol. 288, N 45. – P. 32517–32527. https://doi.org/10.1074/jbc.m113.488387Marzoq A. J., Giese N., Hoheisel J. D., Alhamdani M. S. S. Proteome variations in pancreatic stellate cells upon stimulation with proinflammatory factors. Journal of Biological Chemistry, 2013, vol. 288, no. 45, рр. 32517–32527. https://doi.org/10.1074/jbc.m113.488387Activated perilobular, not periacinar, pancreatic stellate cells contribute to fibrogenesis in chronic alcoholic pancreatitis / K. Suda [et al.] // Pathol. Int. – 2007. – Vol. 57, N 1. – P. 21–25. https://doi.org/10.1111/j.1440-1827.2007.02051.xSuda K., Fukumura Y., Takase M., Kashiwagi S., Izumi M., Kumasaka T., Suzuki F. Activated perilobular, not periacinar, pancreatic stellate cells contribute to fibrogenesis in chronic alcoholic pancreatitis. Pathology International, 2007, vol. 57, no. 1, рр. 21–25. https://doi.org/10.1111/j.1440-1827.2007.02051.xPathophysiology of chronic pancreatitis / C. Brock [et al.] // World J. Gastroenterol. – 2013. – Vol. 19, N 42. – P. 7231–7240. https://doi.org/10.3748/wjg.v19.i42.7231Brock C., Nielsen L. M., Lelic D., Drewes A. M. Pathophysiology of chronic pancreatitis. World Journal of Gastro enterology, 2013, vol. 19, no. 42, рр. 7231–7240. https://doi.org/10.3748/wjg.v19.i42.7231Study on free radicals and pancreatic fibrosis-pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor / N. Matsumura [et al.] // Pancreas. – 2001. – Vol. 22, N 1. – P. 53–57. https://doi.org/10.1097/00006676-200101000-00009Matsumura N., Ochi K., Ichimura M., Mizushima T., Harada H., Harada M. Study on free radicals and pancreatic fibrosis-pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor. Pancreas, 2001, vol. 22, no. 1, рр. 53–57. https://doi.org/10.1097/00006676-200101000-00009Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines / H. Aoki [et al.] // Am. J. Physiol. Cell Physiol. – 2007. – Vol. 292, N 1. – P. C259–C268. https://doi.org/10.1152/ajpcell.00030.2006Aoki H., Ohnishi H., Hama K., Shinozaki S., Kita H., Osawa H., Yamamoto H., Sato K., Tamada K., Sugano K. Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines. American Journal of Physiology – Cell Physiology, 2007, vol. 292, no. 1, рр. C259–C268. https://doi.org/10.1152/ajpcell.00030.2006Shimizu, K. Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis / K. Shimizu // J. Gastroenterology. – 2008. – Vol. 43, N 11. – P. 823–832. https://doi.org/10.1007/s00535-008-2249-7Shimizu K. Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis. Journal of Gastroenterology, 2008, vol. 43, no. 11, рр. 823–832. https://doi.org/10.1007/s00535-008-2249-7Ингибирование активированных панкреатических звездчатых клеток (витаминами А и Е) для предупреждения фиброза поджелудочной железы в модели хронического алкогольного панкреатита / М. Е. Ничитайло [и др.] // Морфологiя. – 2012. – Т. 6, № 2. – С. 34–41.Nichitailo M. E., Kravchenko D. A., Medvetskii E. B., Shpon’ka I. S., Savitskaya I. M. Inhibition of pancreatic stellate cell activation by the vitamin A and vitamin E as a therapy for prevention fibrogenesis in experimental chronic alcoholic pancreatic. Morfologiya [Morphology], 2012, vol. 6, no. 2, рр. 34–41 (in Russian).Talukdar, R. Pancreatic stellate cells: new target in the treatment of chronic pancreatitis / R. Talukdar, R. K. Tandon // J. Gastroenterol. Hepatol. – 2008. – Vol. 23, N 1. – P. 34–41. https://doi.org/10.1111/j.1440-1746.2007.05206.xTalukdar R., Tandon R. K. Pancreatic stellate cells: new target in the treatment of chronic pancreatitis. Journal of Gastroenterology and Hepatology, 2008, vol. 23, no. 1, рр. 34–41. https://doi.org/10.1111/j.1440-1746.2007.05206.xSenescence determines the fate of activated rat pancreatic stellate cells / B. Fitzner [et al.] // J. Cell. Mol. Med. – 2012. – Vol. 16, N 11. – P. 2620–2630. https://doi.org/10.1111/j.1582-4934.2012.01573.xFitzner B., Müller S., Walther M., Fischer M., Engelmann R., Müller-Hilke B., Pützer B. M., Kreutzer M., Nizze H., Jaster R. Senescence determines the fate of activated rat pancreatic stellate cells. Journal of Cellular and Molecular Medicine, 2012, vol. 16, no. 11, рр. 2620–2630. https://doi.org/10.1111/j.1582-4934.2012.01573.xActivation of pancreatic stellate cells involves an EMT-like process / L. Tian [et al.] // Inter. J. Oncol. – 2016. – Vol. 48, N 2. – P. 783–792. https://doi.org/10.3892/ijo.2015.3282Tian L., Lu Z.-P., Cai B.-B., Zhao L.-T., Qian D., Xu Q.-Ch., Wu P.-F., Zhu Y., Zhang J.-J., Du Q., Miao Y., Jiang K.-R. Activation of pancreatic stellate cells involves an EMT-like process. International Journal of Oncology, 2016, vol. 48, no. 2, рр. 783–792. https://doi.org/10.3892/ijo.2015.3282Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions / G. Pearson [et al.] // Endocr. Rev. – 2001. – Vol. 22, N 2. – P. 153–183. https://doi.org/10.1210/er.22.2.153Pearson G., Robinson F., Beers Gibson T., Xu B., Karandikar M., Berman K., Cobb M. H. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine Reviews. 2001, vol. 22, no. 2, рр. 153–183. https://doi.org/10.1210/er.22.2.153Masamune, A. Signal transduction in pancreatic stellate cells / A. Masamune, T. Shimosegawa // J. Gastroenterol. – 2009. – Vol. 44, N 4. – P. 249–260. https://doi.org/10.1007/s00535-009-0013-2Masamune A., Shimosegawa T. Signal transduction in pancreatic stellate cells. Journal of Gastroenterology, 2009, vol. 44, no. 4, рр. 249–260. https://doi.org/10.1007/s00535-009-0013-2Pancreatic stellate cell activation by ethanol and acetaldehyde: is it mediated by the mitogen-activated protein kinase signaling pathway? / J. A. McCarroll [et al.] // Pancreas. – 2003. – Vol. 27, N 2. – P. 150–160. https://doi.org/10.1097/00006676-200308000-00008McCarroll J. A., Phillips P. A., Park S., Doherty E., Pirola R. C., Wilson J. S., Apte M. V. Pancreatic stellate cell activation by ethanol and acetaldehyde: is it mediated by the mitogen-activated protein kinase signaling pathway? Pancreas, 2003, vol. 27, no. 2, рр. 150–160. ttps://doi.org/10.1097/00006676-200308000-00008Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming growth factor-beta1 regulation of pancreatic stellate cellular functions / H. Ohnishi [et al.] // J. Biol. Chem. – 2003. – Vol. 279, N 10. – P. 8873–8878. https://doi.org/10.1074/jbc.m309698200Ohnishi H., Miyata T., Yasuda H., Satoh Y., Hanatsuka K., Kita H., Ohashi A., Tamada K., Makita N., Iiri T., Ueda N., Mashima H., Sugano K. Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming growth factor-beta1 regulation of pancreatic stellate cellular functions. Journal of Biological Chemistry, 2003, vol. 279, no. 10, рр. 8873–8878. https://doi.org/10.1074/jbc.m309698200

The authors declare that there are no conflicts of interest present.