Insulin-like Growth Factor and Epidermal Growth Factor Treatment: New Approaches to Protecting Steatotic Livers Against Ischemia-reperfusion Injury

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2009 Mar 14

PMID 19282385

Citations 12

Authors

Arani Casillas-Ramirez

Amine Zaouali

Susagna Padrissa-Altes

Ismail Ben Mosbah

Anna Pertosa

Izabel Alfany-Fernandez

Maria Bintanel-Morcillo

Carme Xaus

Antoni Rimola

Juan Rodes

Joan Rosello-Catafau

Carmen Peralta

Affiliations

Soon will be listed here.

Abstract

Hepatic steatosis is a major risk factor in ischemia-reperfusion (I/R). IGF-binding proteins (IGFBPs) modulate IGF-I action by transporting circulating IGF-I to its sites of action. Epidermal growth factor (EGF) stimulates IGF-I synthesis in vitro. We examined the effect of IGF-I and EGF treatment, separately or in combination, on the vulnerability of steatotic livers to I/R. Our results indicated that I/R impaired IGF-I synthesis only in steatotic livers. Only when a high dose of IGF-I (400 microg/kg) was given to obese animals did they show high circulating IGF-I:IGFBP levels, increased hepatic IGF-I levels, and protection against damage. In lean animals, a dose of 100 microg/kg IGF-I protected nonsteatotic livers. Our results indicated that the combined administration of IGF-I and EGF resulted in hepatic injury parameters in both liver types similar to that obtained by IGF-I and EGF separately. IGF-I increased egf expression in both liver types. The beneficial role of EGF on hepatic I/R injury may be attributable to p38 inhibition in nonsteatotic livers and to PPAR gamma overexpression in steatotic livers. In conclusion, IGF-I and EGF may constitute new pharmacological strategies to reduce the inherent susceptibility of steatotic livers to I/R injury.

Citing Articles

Novel, Innovative Models to Study Ischemia/Reperfusion-Related Redox Damage in Organ Transplantation.

Hofmann J, Puhringer M, Steinkellner S, Holl A, Meszaros A, Schneeberger S Antioxidants (Basel). 2023; 12(1).

PMID: 36670893 PMC: 9855021. DOI: 10.3390/antiox12010031.

The Role of Neuregulin-1 in Steatotic and Non-Steatotic Liver Transplantation from Brain-Dead Donors.

Mico-Carnero M, Casillas-Ramirez A, Sanchez-Gonzalez A, Rojano-Alfonso C, Peralta C Biomedicines. 2022; 10(5).

PMID: 35625715 PMC: 9138382. DOI: 10.3390/biomedicines10050978.

Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors.

Mico-Carnero M, Casillas-Ramirez A, Caballeria-Casals A, Rojano-Alfonso C, Sanchez-Gonzalez A, Peralta C Nutrients. 2021; 13(8).

PMID: 34444713 PMC: 8400262. DOI: 10.3390/nu13082554.

TSLP protects against liver I/R injury via activation of the PI3K/Akt pathway.

Li S, Yi Z, Deng M, Scott M, Yang C, Li W JCI Insight. 2019; 4(22).

PMID: 31723054 PMC: 6948857. DOI: 10.1172/jci.insight.129013.

Mitogen Activated Protein Kinases in Steatotic and Non-Steatotic Livers Submitted to Ischemia-Reperfusion.

Jimenez-Castro M, Cornide-Petronio M, Gracia-Sancho J, Casillas-Ramirez A, Peralta C Int J Mol Sci. 2019; 20(7).

PMID: 30974915 PMC: 6479363. DOI: 10.3390/ijms20071785.

References

Canelo R, Braun F, Sattler B, Klinge B, Lorf T, Ramadori G . Is a fatty liver dangerous for transplantation?. Transplant Proc. 1999; 31(1-2):414-5. DOI: 10.1016/s0041-1345(98)01685-6. View

Lang C, Liu X, Nystrom G, Frost R . Acute response of IGF-I and IGF binding proteins induced by thermal injury. Am J Physiol Endocrinol Metab. 2000; 278(6):E1087-96. DOI: 10.1152/ajpendo.2000.278.6.E1087. View

Angulo P . Nonalcoholic fatty liver disease. N Engl J Med. 2002; 346(16):1221-31. DOI: 10.1056/NEJMra011775. View

Takaoka M, Smith C, Mashiba M, Okawa T, Andl C, El-Deiry W . EGF-mediated regulation of IGFBP-3 determines esophageal epithelial cellular response to IGF-I. Am J Physiol Gastrointest Liver Physiol. 2005; 290(2):G404-16. PMC: 2996094. DOI: 10.1152/ajpgi.00344.2005. View

Casillas-Ramirez A, Amine-Zaouali M, Massip-Salcedo M, Padrissa-Altes S, Bintanel-Morcillo M, Ramalho F . Inhibition of angiotensin II action protects rat steatotic livers against ischemia-reperfusion injury. Crit Care Med. 2008; 36(4):1256-66. DOI: 10.1097/CCM.0b013e31816a023c. View

DAlessandro A, Kalayoglu M, Sollinger H, Hoffmann R, Reed A, Knechtle S . The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation. Transplantation. 1991; 51(1):157-63. DOI: 10.1097/00007890-199101000-00024. View

Castilla-Cortazar I, Picardi A, Tosar A, Ainzua J, Urdaneta E, Garcia M . Effect of insulin-like growth factor I on in vivo intestinal absorption of D-galactose in cirrhotic rats. Am J Physiol. 1999; 276(1):G37-42. DOI: 10.1152/ajpgi.1999.276.1.G37. View

Zhou Y, Zheng S, Lin J, Zhang Q, Chen A . The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro. Lab Invest. 2007; 87(5):488-98. DOI: 10.1038/labinvest.3700532. View

Camargo Jr C, Madden J, Gao W, Selvan R, Clavien P . Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatology. 1997; 26(6):1513-20. DOI: 10.1002/hep.510260619. View

10.

Shaikh S, Bloomfield F, Bauer M, Phua H, Gilmour R, Harding J . Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues. J Endocrinol. 2005; 186(1):145-55. DOI: 10.1677/joe.1.06113. View

11.

Nolan C, Leahy J, Delghingaro-Augusto V, Moibi J, Soni K, Peyot M . Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling. Diabetologia. 2006; 49(9):2120-30. DOI: 10.1007/s00125-006-0305-5. View

12.

Holt R, Baker A, Miell J . The pathogenesis of growth failure in paediatric liver disease. J Hepatol. 1997; 27(2):413-23. DOI: 10.1016/s0168-8278(97)80190-0. View

13.

Donaghy A, BAXTER R . Insulin-like growth factor bioactivity and its modification in growth hormone resistant states. Baillieres Clin Endocrinol Metab. 1996; 10(3):421-46. DOI: 10.1016/s0950-351x(96)80560-x. View

14.

Vetelainen R, van Vliet A, Gouma D, van Gulik T . Steatosis as a risk factor in liver surgery. Ann Surg. 2007; 245(1):20-30. PMC: 1867945. DOI: 10.1097/01.sla.0000225113.88433.cf. View

15.

Holt R, Crossey P, Jones J, Baker A, Portmann B, Miell J . Hepatic growth hormone receptor, insulin-like growth factor I, and insulin-like growth factor-binding protein messenger RNA expression in pediatric liver disease. Hepatology. 1997; 26(6):1600-6. DOI: 10.1002/hep.510260631. View

16.

Chen J, Nielsen M, Caumo A, Vilstrup H, Christiansen J, Frystyk J . Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis. Eur J Endocrinol. 2006; 155(2):285-92. DOI: 10.1530/eje.1.02218. View

17.

Farrell G, Teoh N, McCuskey R . Hepatic microcirculation in fatty liver disease. Anat Rec (Hoboken). 2008; 291(6):684-92. DOI: 10.1002/ar.20715. View

18.

Chen X, Ferry Jr R . Novel actions of IGFBP-3 on intracellular signaling pathways of insulin-secreting cells. Growth Horm IGF Res. 2005; 16(1):41-8. PMC: 3092594. DOI: 10.1016/j.ghir.2005.09.003. View

19.

Goda N, Tenno T, Inomata K, Shirakawa M, Tanaka T, Hiroaki H . Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5. Exp Cell Res. 2008; 314(13):2352-61. DOI: 10.1016/j.yexcr.2008.05.008. View

20.

Bhattacharyya N, Pechhold K, Shahjee H, Zappala G, Elbi C, Raaka B . Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. J Biol Chem. 2006; 281(34):24588-601. DOI: 10.1074/jbc.M509463200. View