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http://dx.doi.org/10.5653/cerm.2020.04035

Transforming growth factor-beta and liver injury in an arginine vasopressin-induced pregnant rat model  

Govender, Nalini (Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology)
Ramdin, Sapna (Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology)
Reddy, Rebecca (Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology)
Naicker, Thajasvarie (Discipline of Optics and Imaging, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal)
Publication Information
Clinical and Experimental Reproductive Medicine / v.48, no.2, 2021 , pp. 124-131 More about this Journal
Abstract
Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model. Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.
Keywords
Arginase 1; Arginine vasopressin; Aspartate transaminase 1; Liver injury; Transforming growth factor beta;
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1 Drawz PE, Rosenberg ME. Slowing progression of chronic kidney disease. Kidney Int Suppl (2011) 2013;3:372-6.   DOI
2 Huber A, Hefler L, Tempfer C, Zeisler H, Lebrecht A, Husslein P. Transforming growth factor-beta 1 serum levels in pregnancy and pre-eclampsia. Acta Obstet Gynecol Scand 2002;81:168-71.   DOI
3 Sandgren JA, Deng G, Linggonegoro DW, Scroggins SM, Perschbacher KJ, Nair AR, et al. Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice. JCI Insight 2018;3:e99403.   DOI
4 Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 2005;5:641-54.   DOI
5 Harmon AC, Cornelius DC, Amaral LM, Faulkner JL, Cunningham MW Jr, Wallace K, et al. The role of inflammation in the pathology of preeclampsia. Clin Sci (Lond) 2016;130:409-19.   DOI
6 Bagnost T, Berthelot A, Alvergnas M, Miguet-Alfonsi C, Andre C, Guillaume Y, et al. Misregulation of the arginase pathway in tissues of spontaneously hypertensive rats. Hypertens Res 2009;32:1130-5.   DOI
7 Louis CA, Mody V, Henry WL Jr, Reichner JS, Albina JE. Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages. Am J Physiol 1999;276:R237-42.
8 Munder M, Eichmann K, Moran JM, Centeno F, Soler G, Modolell M. Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J Immunol 1999;163:3771-7.
9 Shaarawy M, El Meleigy M, Rasheed K. Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a potential biomarker for the assessment of disease severity and fetal outcome. J Soc Gynecol Investig 2001;8:27-31.   DOI
10 Perucci LO, Gomes KB, Freitas LG, Godoi LC, Alpoim PN, Pinheiro MB, et al. Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia. PLoSOne 2014;9:e97632.   DOI
11 Peracoli MT, Menegon FT, Borges VT, de Araujo Costa RA, Thomazini-Santos IA, et al. Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia. J Reprod Immunol 2008;79:79-84.   DOI
12 Gregory AL, Xu G, Sotov V, Letarte M. Review: the enigmatic role of endoglin in the placenta. Placenta 2014;35 Suppl:S93-9.   DOI
13 Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, et al. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003;108:2000-6.   DOI
14 Toque HA, Nunes KP, Rojas M, Bhatta A, Yao L, Xu Z, et al. Arginase 1 mediates increased blood pressure and contributes to vascular endothelial dysfunction in deoxycorticosterone acetate-salt hypertension. Front Immunol 2013;4:219.   DOI
15 Chang CI, Zoghi B, Liao JC, Kuo L. The involvement of tyrosine kinases, cyclic AMP/protein kinase A, and p38 mitogen-activated protein kinase in IL-13-mediated arginase I induction in macrophages: its implications in IL-13-inhibited nitric oxide production. J Immunol 2000;165:2134-41.   DOI
16 Alese MO, Moodley J, Naicker T. Preeclampsia and HELLP syndrome, the role of the liver. J Matern Fetal Neonatal Med 2021;34:117-23.   DOI
17 Vallee A, Lecarpentier Y. TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts. Cell Biosci 2019;9:98.   DOI
18 Toporsian M, Gros R, Kabir MG, Vera S, Govindaraju K, Eidelman DH, et al. A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res 2005;96:684-92.   DOI
19 Froese AR, Shimbori C, Bellaye PS, Inman M, Obex S, Fatima S, et al. Stretch-induced activation of transforming growth factor-β1 in pulmonary fibrosis. Am J Respir Crit Care Med 2016;194:84-96.   DOI
20 Piera-Velazquez S, Mendoza FA, Jimenez SA. Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of human fibrotic diseases. J Clin Med 2016;5:45.   DOI
21 Dixon TF, Purdom M. Serum 5-nucleotidase. J Clin Pathol 1954;7:341-3.   DOI
22 Hyder MA, Hasan M, Mohieldein A. Comparative study of 5'-nucleotidase test in various liver diseases. J Clin Diagn Res 2016;10:BC01-3.
23 Li Q. Transforming growth factor β signaling in uterine development and function. J Anim Sci Biotechnol 2014;5:52.   DOI
24 Lyall F, Simpson H, Bulmer JN, Barber A, Robson SC. Transforming growth factor-beta expression in human placenta and placental bed in third trimester normal pregnancy, preeclampsia, and fetal growth restriction. Am J Pathol 2001;159:1827-38.   DOI
25 Girling JC, Dow E, Smith JH. Liver function tests in pre-eclampsia: importance of comparison with a reference range derived for normal pregnancy. Br J Obstet Gynaecol 1997;104:246-50.   DOI
26 Caniggia I, Grisaru-Gravnosky S, Kuliszewsky M, Post M, Lye SJ. Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest 1999;103:1641-50.   DOI
27 Scroggins SM, Santillan DA, Lund JM, Sandgren JA, Krotz LK, Hamilton WS, et al. Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia. Clin Sci (Lond) 2018;132:419-36.   DOI
28 Schutt VA, Minuk GY. Liver diseases unique to pregnancy. Best Pract Res Clin Gastroenterol 2007;21:771-92.   DOI
29 Chambaz EM, Souchelnitskiy S, Pellerin S, Defaye G, Cochet C, Feige JJ. Transforming growth factors-beta s: a multifunctional cytokine family: implication in the regulation of adrenocortical cell endocrine functions. Horm Res 1996;45:222-6.   DOI
30 Westbrook RH, Dusheiko G, Williamson C. Pregnancy and liver disease. J Hepatol 2016;64:933-45.   DOI
31 Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J 2009;3:17.
32 Lafontaine L, Chaudhry P, Lafleur MJ, Van Themsche C, Soares MJ, Asselin E. Transforming growth factor Beta regulates proliferation and invasion of rat placental cell lines. Biol Reprod 2011;84:553-9.   DOI
33 Carakostas MC, Power RJ, Banerjee AK. Serum 5'nucleotidase activity in rats: a method for automated analysis and criteria for interpretation. Vet Clin Pathol 1990;19:109-113.   DOI
34 Shekhar S, Diddi G. Liver disease in pregnancy. Taiwan J Obstet Gynecol 2015;54:475-82.   DOI
35 Landmesser U, Drexler H. Endothelial function and hypertension. Curr Opin Cardiol 2007;22:316-20.   DOI
36 Arika WM, Nyamai DW, Osano KO, Ngugi MP, Njagi EN. Biochemical markers of in vivo hepatotoxicity. J Clin Toxicol 2016;6:e1000297.
37 Douillet CD, Velarde V, Christopher JT, Mayfield RK, Trojanowska ME, Jaffa AA. Mechanisms by which bradykinin promotes fibrosis in vascular smooth muscle cells: role of TGF-beta and MAPK. Am J Physiol Heart Circ Physiol 2000;279:H2829-37.   DOI
38 Bremer L, Schramm C, Tiegs G. Immunology of hepatic diseases during pregnancy. Semin Immunopathol 2016;38:669-85.   DOI
39 Valensise H, Vasapollo B, Gagliardi G, Novelli GP. Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension 2008;52:873-80.   DOI
40 Aggarwal PK, Chandel N, Jain V, Jha V. The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia. J Hum Hypertens 2012;26:236-41.   DOI
41 Mikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, et al. Liver disease during pregnancy: a challenging clinical issue. Med Sci Monit 2018;24:4080-90.   DOI
42 Frishman WH, Schlocker SJ, Awad K, Tejani N. Pathophysiology and medical management of systemic hypertension in pregnancy. Cardiol Rev 2005;13:274-84.   DOI
43 Koyama Y, Brenner DA. Liver inflammation and fibrosis. J Clin Invest 2017;127:55-64.   DOI
44 Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension 2018;72:24-43.   DOI
45 Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis 2006;9:225-30.   DOI
46 August P, Leventhal B, Suthanthiran M. Hypertension-induced organ damage in African Americans: transforming growth factor-beta(1) excess as a mechanism for increased prevalence. Curr Hypertens Rep 2000;2:184-91.   DOI
47 Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672-83.   DOI
48 Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006;12:642-9.   DOI
49 Adu-Gyamfi EA, Lamptey J, Duan F, Wang YX, Ding YB. The transforming growth factor β superfamily as possible biomarkers of pre-eclampsia: a comprehensive review. Biomark Med 2019;13:1321-30.   DOI
50 Munger JS, Sheppard D. Cross talk among TGF-β signaling pathways, integrins, and the extracellular matrix. Cold Spring Harb Perspect Biol 2011;3:a005017.   DOI
51 Dooley S, ten Dijke P. TGF-β in progression of liver disease. Cell Tissue Res 2012;347:245-56.   DOI
52 Bankir L, Bichet DG, Morgenthaler NG. Vasopressin: physiology, assessment 0and osmosensation. J Intern Med 2017;282:284-97.   DOI
53 Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol 2018;218(2S):S745-61.   DOI
54 Adu-Gyamfi EA, Ding YB, Wang YX. Regulation of placentation by the transforming growth factor beta superfamily. Biol Reprod 2020;102:18-26.   DOI
55 Santillan MK, Santillan DA, Scroggins SM, Min JY, Sandgren JA, Pearson NA, et al. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model. Hypertension 2014;64:852-9.   DOI
56 Bourque CW. Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci 2008;9:519-31.   DOI