دورية أكاديمية
Effects of erythropoietin receptor activity on angiogenesis, tubular injury, and fibrosis in acute kidney injury: a "U-shaped" relationship.
| العنوان: | Effects of erythropoietin receptor activity on angiogenesis, tubular injury, and fibrosis in acute kidney injury: a "U-shaped" relationship. |
|---|---|
| المؤلفون: | Shi M; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas., Flores B; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas., Li P; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas.; Department of Nephrology, Yu-Huang-Ding Hospital, Qingdao University , Yantai, Shandong , People's Republic of China., Gillings N; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas., McMillan KL; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas., Ye J; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas., Huang LJ; Department of Cell Biology, University of Texas Southwestern Medical Center , Dallas, Texas., Sidhu SS; Banting and Best Department of Medical Research and Department of Molecular Genetics, The Donnelly Centre, University of Toronto , Toronto, Ontario , Canada., Zhong YP; Pape Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University , Portland, Oregon., Grompe MT; Pape Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University , Portland, Oregon., Streeter PR; Pape Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University , Portland, Oregon., Moe OW; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas.; Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, Texas.; Department of Physiology, University of Texas Southwestern Medical Center , Dallas, Texas., Hu MC; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center , Dallas, Texas.; Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, Texas. |
| المصدر: | American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2018 Apr 01; Vol. 314 (4), pp. F501-F516. Date of Electronic Publication: 2017 Nov 29. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901990 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1466 (Electronic) Linking ISSN: 15221466 NLM ISO Abbreviation: Am J Physiol Renal Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, c1997- |
| مواضيع طبية MeSH: | Neovascularization, Physiologic*, Acute Kidney Injury/*metabolism , Capillaries/*metabolism , Erythropoietin/*metabolism , Kidney Tubules, Proximal/*blood supply , Kidney Tubules, Proximal/*metabolism , Receptors, Erythropoietin/*metabolism, Acute Kidney Injury/genetics ; Acute Kidney Injury/pathology ; Acute Kidney Injury/physiopathology ; Animals ; Apoptosis ; Autophagy ; Capillaries/pathology ; Capillaries/physiopathology ; Cell Hypoxia ; Cells, Cultured ; Disease Models, Animal ; Fibrosis ; Humans ; Kidney Tubules, Proximal/pathology ; Kidney Tubules, Proximal/physiopathology ; Mice, 129 Strain ; Mice, Transgenic ; Receptors, Erythropoietin/deficiency ; Receptors, Erythropoietin/genetics ; Signal Transduction |
| مستخلص: | The erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knockin of wild-type human EpoR, which is hypofunctional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, more apoptosis at the acute stage (<7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days). In contrast, mice with hyperactive EpoR signaling from knockin of a constitutively active human EpoR had higher autophagic flux, milder kidney damage, and better renal function at the acute stage but, surprisingly, worse tubulointerstitial fibrosis and renal function at the subacute stage. Either excess or deficient EpoR activity in the kidney was associated with abnormal peritubular capillaries and tubular hypoxia, creating a "U-shaped" relationship. The direct effects of EpoR on tubular cells were confirmed in vitro by a hydrogen peroxide model using primary cultured proximal tubule cells with different EpoR activities. In summary, normal erythropoietin (EPO)/EpoR signaling in renal tubules provides defense against renal tubular injury maintains the autophagy-apoptosis balance and peritubular capillary integrity. High and low EPO/EpoR bioactivities both lead to vascular defect, and high EpoR activity overides the tubular protective effects in AKI recovery. |
| References: | Am J Physiol Renal Physiol. 2014 Mar 15;306(6):F681-92. (PMID: 24402097) Kidney Int. 2013 Sep;84(3):468-81. (PMID: 23636173) Mol Cell. 2008 Jun 20;30(6):678-88. (PMID: 18570871) Adv Pharmacol. 2010;60:257-85. (PMID: 21081221) Crit Care. 2015 Sep 18;19:332. (PMID: 26384003) J Am Soc Nephrol. 2015 May;26(5):1027-38. (PMID: 25385849) Bone. 2011 Nov;49(5):1037-45. (PMID: 21851867) Nephrol Dial Transplant. 2009 Nov;24(11):3349-54. (PMID: 19474273) J Dent Res. 2015 Mar;94(3):455-63. (PMID: 25586589) Crit Care. 2013 Oct 24;17(5):R254. (PMID: 24156702) Anesthesiology. 2010 Feb;112(2):395-405. (PMID: 20068453) Semin Nephrol. 2014 Jul;34(4):404-17. (PMID: 25217269) Exp Ther Med. 2015 Feb;9(2):559-562. (PMID: 25574234) Circ Res. 2007 Mar 16;100(5):662-9. (PMID: 17293480) Autophagy. 2008 Jul;4(5):710-2. (PMID: 18497570) FASEB J. 2010 Sep;24(9):3438-50. (PMID: 20466874) J Transl Med. 2015 Nov 10;13:355. (PMID: 26554357) PLoS One. 2012;7(1):e29893. (PMID: 22235348) Am J Pathol. 2014 Apr;184(4):1230-1239. (PMID: 24630601) Cell Cycle. 2008 May 1;7(9):1128-32. (PMID: 18418042) Crit Rev Oncol Hematol. 2007 Nov;64(2):159-71. (PMID: 17482474) Kidney Int. 2001 Jan;59(1):246-51. (PMID: 11135077) Nephrol Dial Transplant. 2005 Jun;20(6):1025-8. (PMID: 15840686) Mol Neurobiol. 2016 Aug;53(6):3812-3821. (PMID: 26156288) Curr Neurovasc Res. 2016;13(4):329-340. (PMID: 27488211) Nephron Clin Pract. 2014;127(1-4):56-60. (PMID: 25343822) PLoS One. 2015 Mar 25;10(3):e0122149. (PMID: 25807104) Cell Death Differ. 2004 Jul;11 Suppl 1:S37-44. (PMID: 15243580) Kidney Int. 2006 Jul;70(2):246-50. (PMID: 16738535) Am J Physiol Renal Physiol. 2008 Dec;295(6):F1689-95. (PMID: 18815218) Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3513-8. (PMID: 23401545) Kidney Int. 2013 Sep;84(3):482-90. (PMID: 23594675) Am J Physiol Renal Physiol. 2011 Mar;300(3):F721-33. (PMID: 21123492) Kidney Int. 2008 Feb;73(4):430-45. (PMID: 18046317) J Am Soc Nephrol. 2002 Jul;13(7):1837-46. (PMID: 12089379) Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3974-8. (PMID: 8171022) Transplant Proc. 2016 Jan-Feb;48(1):217-21. (PMID: 26915871) Kidney Int. 2013 Sep;84(3):427-9. (PMID: 23989353) Am J Physiol. 1997 Dec;273(6 Pt 2):R1829-44. (PMID: 9435635) Semin Nephrol. 2010 May;30(3):268-77. (PMID: 20620671) Blood. 2015 Jun 4;125(23):3536-41. (PMID: 25887776) Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):986-91. (PMID: 11158582) Eur Heart J. 2004 Feb;25(4):285-91. (PMID: 14984916) Nephrol Dial Transplant. 2004 Feb;19(2):348-55. (PMID: 14736958) J Clin Invest. 2008 Feb;118(2):526-33. (PMID: 18219389) J Am Soc Nephrol. 2014 Sep;25(9):1924-31. (PMID: 24652794) J Am Soc Nephrol. 2001 Jul;12(7):1448-57. (PMID: 11423573) Kidney Int. 2008 Sep;74(5):631-40. (PMID: 18509315) Compr Physiol. 2012 Apr;2(2):1303-53. (PMID: 23798302) PLoS One. 2013 Jul 25;8(7):e69620. (PMID: 23936061) Nat Rev Nephrol. 2015 May;11(5):264-76. (PMID: 25643664) Cell. 2005 Sep 23;122(6):927-39. (PMID: 16179260) Kidney Int. 2014 Apr;85(4):855-70. (PMID: 24304882) J Clin Invest. 2011 Nov;121(11):4210-21. (PMID: 22045571) Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H331-40. (PMID: 16024562) Proc Natl Acad Sci U S A. 1990 Aug;87(15):5978-82. (PMID: 2165612) Kidney Int. 2010 Dec;78(12 ):1240-51. (PMID: 20861825) Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4635-40. (PMID: 9539790) J Am Soc Nephrol. 2015 Jun;26(6):1290-302. (PMID: 25326585) Ann Intensive Care. 2011 Mar 21;1(1):3. (PMID: 21906325) PLoS One. 2017 Sep 8;12 (9):e0181848. (PMID: 28886014) Cell Rep. 2014 Apr 10;7(1):194-207. (PMID: 24703840) J Clin Invest. 2010 Sep;120(9):3022-32. (PMID: 20811158) Am J Pathol. 2011 Feb;178(2):911-23. (PMID: 21281822) J Am Soc Nephrol. 2004 Aug;15(8):2115-24. (PMID: 15284297) J Am Soc Nephrol. 2011 Jan;22(1):124-36. (PMID: 21115613) J Biol Chem. 2009 Jan 30;284(5):2719-28. (PMID: 19029119) Nephron Exp Nephrol. 2010;115(3):e46-59. (PMID: 20424483) J Am Soc Nephrol. 2016 Aug;27(8):2331-45. (PMID: 26701976) Compr Physiol. 2013 Apr;3(2):817-31. (PMID: 23720331) J Biol Chem. 2001 Apr 13;276(15):11870-6. (PMID: 11150293) J Biol Chem. 2004 Dec 10;279(50):52282-92. (PMID: 15358759) J Am Soc Nephrol. 2013 Feb;24(2):268-82. (PMID: 23334396) Med Biol Eng Comput. 2012 May;50(5):473-82. (PMID: 22415740) Am J Pathol. 2013 Jul;183(1):160-72. (PMID: 23684791) Fibrogenesis Tissue Repair. 2012 Jun 06;5(Suppl 1):S16. (PMID: 23259746) Mol Med Rep. 2014 Jun;9(6):2061-8. (PMID: 24682292) Methods Mol Biol. 2009;466:161-74. (PMID: 19148611) Shock. 2012 Mar;37(3):289-96. (PMID: 22089196) Am J Physiol Renal Physiol. 2007 Aug;293(2):F476-85. (PMID: 17475898) Autophagy. 2016 Jun 2;12 (6):976-98. (PMID: 27123926) J Neurosci. 2006 Jan 25;26(4):1269-74. (PMID: 16436614) Am J Physiol Regul Integr Comp Physiol. 2010 Nov;299(5):R1387-95. (PMID: 20702799) Biochim Biophys Acta. 2014 Nov;1842(11):2306-17. (PMID: 25220479) Nephrol Dial Transplant. 2011 Apr;26(4):1132-7. (PMID: 21330358) J Am Soc Nephrol. 2011 May;22(5):902-13. (PMID: 21493778) J Biomed Biotechnol. 2010;2010:395785. (PMID: 20454536) Br J Ophthalmol. 2007 Oct;91(10):1376-8. (PMID: 17522145) Dis Model Mech. 2013 Jul;6(4):1021-30. (PMID: 23519033) Kidney Int. 2004 Aug;66(2):683-95. (PMID: 15253723) Curr Heart Fail Rep. 2007 Sep;4(3):127-33. (PMID: 17883987) J Signal Transduct. 2011;2011:768512. (PMID: 21776388) Int J Mol Sci. 2012 Oct 10;13(10 ):12939-51. (PMID: 23202931) J Biol Chem. 2002 Jan 18;277(3):2040-9. (PMID: 11696540) Blood. 2006 Mar 1;107(5):1892-5. (PMID: 16249375) PLoS One. 2013 Aug 05;8(8):e70464. (PMID: 23940580) |
| معلومات مُعتمدة: | R01 DK091392 United States DK NIDDK NIH HHS; R01 DK092461 United States DK NIDDK NIH HHS; R01 HL089966 United States HL NHLBI NIH HHS; U01 HL110964 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: AKI; EpoR; autophagy; peritubular capillary; tubulointerstitial fibrosis |
| المشرفين على المادة: | 0 (Epo protein, mouse) 0 (Receptors, Erythropoietin) 11096-26-7 (Erythropoietin) |
| تواريخ الأحداث: | Date Created: 20171201 Date Completed: 20190422 Latest Revision: 20191008 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5966758 |
| DOI: | 10.1152/ajprenal.00306.2017 |
| PMID: | 29187371 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1466 |
|---|---|
| DOI: | 10.1152/ajprenal.00306.2017 |