Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema.
Aquaporin-4 (AQP4) is a family member of water-channel proteins and is dominantly expressed in the foot process of glial cells surrounding capillaries. The predominant expression at the boundaries between cerebral parenchyma and major fluid compartments suggests the function of aquaporin-4 in water transfer into and out of the brain parenchyma. Accumulating evidences have suggested that the dysregulation of aquaporin-4 relates to the brain edema resulting from a variety of neuro-disorders, such as ischemic or hemorrhagic stroke, trauma, etc. During edema formation in the brain, aquaporin-4 has been shown to contribute to the astrocytic swelling, while in the resolution phase, it has been seen to facilitate the reabsorption of extracellular fluid. In addition, aquaporin-4-deficient mice are protected from cytotoxic edema produced by water intoxication and brain ischemia. However, aquaporin-4 deletion exacerbates vasogenic edema in the brain of different pathological disorders. Recently, our published data showed that the upregulation of aquaporin-4 in astrocytes probably contributes to the transition from cytotoxic edema to vasogenic edema. In this review, apart from the traditional knowledge, we also introduce our latest findings about the effects of mesenchymal stem cells (MSCs) and microRNA-29b on aquaporin-4, which could provide powerful intervention tools targeting aquaporin-4.
Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China. shtangguanghui@163.com.
Guanghui
G
Tang
Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China. gyyang0626@163.com.
Guo-Yuan
GY
Yang
aquaporin-4; brain edema; therapeutic target; water channel
FASEB J. 2004 Aug;18(11):1291-3
15208268
Glia. 2007 Jul;55(9):935-41
17437301
J Biol Chem. 2005 Apr 8;280(14):13906-12
15695511
Structure. 2006 Sep;14(9):1411-23
16962972
Am J Physiol. 1994 Aug;267(2 Pt 2):H514-20
8067404
Scott Med J. 1978 Jan;23(1):105-6
635527
J Neurotrauma. 2010 Dec;27(12):2147-56
20883153
J Neurosci. 1997 Jan 1;17(1):171-80
8987746
J Matern Fetal Neonatal Med. 2012 Oct;25 Suppl 4:105-7
22958035
Childs Nerv Syst. 1992 Sep;8(6):301-6
1394275
Neurol Sci. 2011 Feb;32(1):113-6
20924629
J Neurosci Res. 2009 May 1;87(6):1435-48
19021292
J Neurosurg. 1962 Jul;19:535-44
14038613
Biochim Biophys Acta. 2009 Jun;1788(6):1213-28
19327343
J Neuroinflammation. 2011 Oct 19;8:143
22011386
Pediatr Nephrol. 2007 Jun;22(6):778-84
17347837
Clin Neurol Neurosurg. 1984;86(2):77-80
6329579
Neurobiol Dis. 1999 Aug;6(4):245-58
10448052
Mol Aspects Med. 2012 Oct-Dec;33(5-6):579-89
22387049
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17815-20
21990350
J Neurosurg. 1955 May;12(3):216-22
14381928
Brain Res. 1987 Nov;433(1):155-9
3676853
Nat Rev Neurosci. 2005 Jun;6(6):484-94
15928718
J Cell Sci. 2005 Dec 15;118(Pt 24):5691-8
16303850
Lancet. 2015 Dec 19;386(10012):2499-506
26452709
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1270-3
17178220
J Clin Invest. 1997 Sep 1;100(5):957-62
9276712
J Biol Chem. 1988 Oct 25;263(30):15634-42
3049610
Nature. 2001 Aug 9;412(6847):641-7
11493922
Cardiovasc Res. 1998 Jul;39(1):106-20
9764193
Bioorg Med Chem. 2009 Jan 1;17(1):418-24
18178093
Glia. 2012 Nov;60(11):1646-59
22782669
J Mol Biol. 2006 Jan 27;355(4):628-39
16325200
Stroke. 2013 Jan;44(1):190-7
23168453
Am J Transl Res. 2016 Jul 15;8(7):3241-50
27508046
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5406-11
19273840
Shock. 2003 Mar;19(3):229-37
12630522
J Biol Chem. 2008 May 30;283(22):15280-6
18375385
J Neurosurg. 2003 Mar;98(3):565-9
12650429
Mol Ther. 2012 Jan;20(1):14-20
22008910
J Neurotrauma. 2011 Mar;28(3):371-81
21204635
Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1602-7
19164545
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):846-51
21187412
Neuroscience. 2004;129(4):1011-20
15561416
J Neurochem. 2006 Oct;99(1):107-18
16987239
J Neuropathol Exp Neurol. 1967 Jan;26(1):1-14
5336776
Stroke Res Treat. 2010 Nov 01;2010:316862
21052549
J Cereb Blood Flow Metab. 2015 Dec;35(12 ):1977-84
26126866
Handb Exp Pharmacol. 2009;(190):159-70
19096776
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13131-6
12232046
CNS Neurosci Ther. 2012 May;18(5):388-94
22533723
Prog Histochem Cytochem. 2004;39(1):1-83
15242101
Trends Cell Biol. 2002 Mar;12(3):112-20
11859023
Exp Neurol. 2002 Mar;174(1):11-20
11869029
Neuroscience. 2010 Apr 28;167(1):60-7
20132873
Neurochem Res. 2015 Feb;40(2):317-28
24996934
Brain Res Mol Brain Res. 2000 May 31;78(1-2):131-7
10891592
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11981-6
9751776
Nat Med. 2000 Feb;6(2):159-63
10655103
J Ethnopharmacol. 2013 Jul 9;148(2):632-9
23707212
Stem Cells. 2014 Dec;32(12):3150-62
25100404
Ulus Travma Acil Cerrahi Derg. 2015 Jul;21(4):235-40
26374408
Vet Clin Pathol. 2012 Mar;41(1):32-44
22250904
Trends Biochem Sci. 1999 Nov;24(11):432-6
10542409
J Neurochem. 2004 Nov;91(4):891-9
15525343
J Exp Med. 2011 Feb 14;208(2):327-39
21300915
Cell Tissue Res. 1999 May;296(2):307-21
10382274