Effects of genistein treatment on molecular markers related to fibrosis: Addition to histological changes in the lung of ovariectomized diabetic rats
Keywords:
Genistein, Menopause, Lung, Fibrosis, TGFβ1Abstract
Objective: Postmenopausal women experience physiological changes in several organs related to estrogen deficiency. On the other hand, the role of estrogen, as a sex hormone, in the physiological function and structure of respiratory system has been stablished. In the present study, we hypothesized that the administration of genistein could reverse lung fibrosis disturbed by estrogen deprivation.
Methods: Forty female sprague–dawley rats were assigned into four groups: rats underwent surgery without ovariectomy (sham), rats that underwent ovariectomies (OVX), ovariectomized rats that were fed with high fat diet (OVX.Dia), ovariectomized diabetic rats with genistein administration (OVX.Dia.Gen). Western blotting technique and hematoxylin & eosin were employed to assess of protein levels and histological changes in the lung.
Results: Transforming growth factor beta-1 and matrix metalloproteinase-2 were found to have differential expression among the groups. Ovariectomy alone and with diabetes increased the levels of growth factor beta-1 and matrix metalloproteinase-2 as compared with the sham (P<0.05). On the other hand, genistein treatment reversed ovariectomy-induced changes in the protein levels as compared with OVX.Dia group (P<0.05).
Conclusion: Genistein ameliorated expression levels of fibrotic biomarkers in the lung of ovariectomized diabetic rats. Our data suggest that genistein may be beneficial for menopausal women through modulation of pulmonary fibrotic biomarkers expression levels.
References
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19. Daghigh F, Alihemmati A, Karimi P, Habibi P, Ahmadiasl N. Fibrotic and apoptotic markers alteration in ovariectomised rats: addition of swimming training preserves lung architecture. Archives of Physiology and Biochemistry, 2017. 7:1-6.
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23. Huang X, Chen S, Xu L, Liu Y, Deb DK, Platanias LC, et al. Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Research, 2005. 65(8): p. 3470-8.
24. Grände M, Franzen Å, Karlsson J-O, Ericson LE, Heldin N-E, Nilsson M. Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes. Journal of Cell Science, 2002. 1159(Pt-22): p. 4227-36.
25. Daghigh F, Alihemmati A, Karimi P, Habibi P, and Ahmadiasl N. Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung. Iranian Journal of Basic Medical Science, 2017. 20(12): p. 1312-7.
26. Kelly LA, O'Leary JJ, Seidlova-Wuttke D, Wuttke W, Norris LA. Genistein alters coagulation gene expression in ovariectomised rats treated with phytoestrogens. Thrombosis and Haemostasis, 2010, 104(6): p. 1250-1257.
27. Cheng W-C, Lo S-C, Tsai K-S, Tu S-T, Wu J-S, Chang C-I, et al. Effects of high-dose phytoestrogens on circulating cellular microparticles and coagulation function in postmenopausal women. Journal of the Formosan Medical Association, 2015. 14(8): p. 710-716.
28. Faramoushi M, Sasan RA, Sarraf VS, Karimi P. Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude. Journal of Cardiovascular and Thoracic Research JCVTR, 2016, 8(1): p. 26-33.
2. Massaro D, Massaro GD. Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2004. 287(6): p. L1154-L9.
3. Elfattah LIA. A comparative study between the effects of dietary soya and estrogen replacement therapy on the lung of ovariectomized albino rats: histological and immunohistochemical study. Egyptian Journal of Histology, 2012. 35(1): p.34-42.
4. Dogru YZ, Nacar T, Unal D, Aksak S, Albayrak A, Odabasoglu F, et al. Effects of diabetes mellitus and postmenopausal period on the lungs of rats. African Journal of Pharmacy and Pharmacology, 2012. 6(27): p.1989-2010.
5. Yeh H-C, Punjabi NM, Wang N-Y, Pankow JS, Duncan BB, Cox CE, et al. Cross-sectional and prospective study of lung function in adults with type 2 diabetes. Diabetes Care, 2008. 31(4): p. 741-746.
6. McGowan TA, Dunn SR, Falkner B, Sharma K. Stimulation of urinary TGF-β and isoprostanes in response to hyperglycemia in humans. Clinical Journal of the American Society of Nephrology, 2006. 1(2): p. 263-268.
7. Bitoska I, Krstevska B, Milenkovic T, Subeska-Stratrova S, Petrovski G, Mishevska SJ, et al. Effects of hormone replacement therapy on insulin resistance in postmenopausal diabetic women. Open Access Macedonian Journal of Medical Sciences, 2016. 4(1): p. 83.
8. Mosca L, Collins P, Herrington DM, Mendelsohn ME, Pasternak RC, Robertson RM, et al. Hormone replacement therapy and cardiovascular disease. Circulation, 2001. 104: p. 499-503.
9. Chen C-L, Weiss NS, Newcomb P, Barlow W, White E. Hormone replacement therapy in relation to breast cancer. Jama, 2002. 287(6): p. 734-41.
10. Serock MR, Wells AK, Khalil RA. Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Patents on Cardiovascular Drug Discovery, 2008. 3(3): p. 165-186.
11. Stephenson T, Setchell K, Kendall C, Jenkins D, Anderson J, Fanti P. Effect of soy protein-rich diet on renal function in young adults with insulin-dependent diabetes mellitus. Clinical Nephrology, 2005. 64(1): p. 1-11.
12. Matori H, Umar S, Nadadur RD, Sharma S, Partow-Navid R, Afkhami M, et al. Genistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats. Hypertension, 2012. 60(2):p. 425-430.
13. Irigoyen MC, Paulini J, Flores LJ, Flues K, Bertagnolli M, Moreira ED, et al. Exercise training improves baroreflex sensitivity associated with oxidative stress reduction in ovariectomized rats. Hypertension, 2005. 46: p. 998-1003.
14. Su X, Meng X, Sun C, Liu L, Su B. Intramuscular injection of soluble receptor for advanced glycation endproducts expression vector prevents the development of streptozotocinâ€induced diabetes mellitus in rats on high fat diet. Journal of diabetes, 2011. 3(4): p. 309-316.
15. Leask A, Abraham DJ. TGF-β signaling and the fibrotic response. FASEB J, 2004. 18(7): p. 816-27.
16. Chambers RC, Leoni P, Kaminski N, Laurent GJ, Heller RA. Global expression profiling of fibroblast responses to transforming growth factor-β 1 reveals the induction of inhibitor of differentiation-1 and provides evidence of smooth muscle cell phenotypic switching. American Journal of Pathology, 2003.162(2): p. 533-546.
17. Jablonska E, Markart P, Zakrzewicz D, Preissner KT, Wygrecka M. Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts. The journal of Biological chemistry, 2010. 285(15): p. 11638-51.
18. Glassberg MK, Choi R, Manzoli V, Shahzeidi S, Rauschkolb P, Voswinckel R, et al. 17β-estradiol replacement reverses age-related lung disease in estrogen-deficient C57BL/6J mice. Endocrinology, 2014. 155(2): p. 441-8.
19. Daghigh F, Alihemmati A, Karimi P, Habibi P, Ahmadiasl N. Fibrotic and apoptotic markers alteration in ovariectomised rats: addition of swimming training preserves lung architecture. Archives of Physiology and Biochemistry, 2017. 7:1-6.
20. Kasai H, Allen JT, Mason RM, Kamimura T, and Zhang Z. TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respiratory Research, 2005. 6(1), p. 56.
21. Lee SW, Song KE, Shin DS, Ahn SM, Ha ES, Kim DJ, et al. Alterations in peripheral blood levels of TIMP-1, MMP-2, and MMP-9 in patients with type-2 diabetes. Diabetes Research and Clinical Practice, 2005. 69(2): p. 175-9.
22. Geiser T. Idiopathic pulmonary fibrosis-a disorder of alveolar wound repair? Swiss Medical Weekly, 2003. 133(29-30): p. 405-11.
23. Huang X, Chen S, Xu L, Liu Y, Deb DK, Platanias LC, et al. Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Research, 2005. 65(8): p. 3470-8.
24. Grände M, Franzen Å, Karlsson J-O, Ericson LE, Heldin N-E, Nilsson M. Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes. Journal of Cell Science, 2002. 1159(Pt-22): p. 4227-36.
25. Daghigh F, Alihemmati A, Karimi P, Habibi P, and Ahmadiasl N. Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung. Iranian Journal of Basic Medical Science, 2017. 20(12): p. 1312-7.
26. Kelly LA, O'Leary JJ, Seidlova-Wuttke D, Wuttke W, Norris LA. Genistein alters coagulation gene expression in ovariectomised rats treated with phytoestrogens. Thrombosis and Haemostasis, 2010, 104(6): p. 1250-1257.
27. Cheng W-C, Lo S-C, Tsai K-S, Tu S-T, Wu J-S, Chang C-I, et al. Effects of high-dose phytoestrogens on circulating cellular microparticles and coagulation function in postmenopausal women. Journal of the Formosan Medical Association, 2015. 14(8): p. 710-716.
28. Faramoushi M, Sasan RA, Sarraf VS, Karimi P. Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude. Journal of Cardiovascular and Thoracic Research JCVTR, 2016, 8(1): p. 26-33.
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Published
2018-09-26
How to Cite
Alipour, M. R., Ahmadiasl, N., Karimi, P., Alihemmati, A., Majidi Zolbin, M., & Daghigh, F. (2018). Effects of genistein treatment on molecular markers related to fibrosis: Addition to histological changes in the lung of ovariectomized diabetic rats. Journal of Contemporary Medical Sciences, 4(3). Retrieved from https://jocms.org/index.php/jcms/article/view/454
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