Human kidney pericytes produce renin.
Pericytes, perivascular cells embedded in the microvascular wall, are crucial for vascular homeostasis. These cells also play diverse roles in tissue development and regeneration as multi-lineage progenitors, immunomodulatory cells and as sources of trophic factors. Here, we establish that pericytes are renin producing cells in the human kidney. Renin was localized by immunohistochemistry in CD146 and NG2 expressing pericytes, surrounding juxtaglomerular and afferent arterioles. Similar to pericytes from other organs, CD146+CD34-CD45-CD56-renal fetal pericytes, sorted by flow cytometry, exhibited tri-lineage mesodermal differentiation potential in vitro. Additionally, renin expression was triggered in cultured kidney pericytes by cyclic AMP as confirmed by immuno-electron microscopy, and secretion of enzymatically functional renin, capable of generating angiotensin I. Pericytes derived from second trimester human placenta also expressed renin in an inducible fashion although the renin activity was much lower than in renal pericytes. Thus, our results confirm and extend the recently discovered developmental plasticity of microvascular pericytes, and may open new perspectives to the therapeutic regulation of the renin-angiotensin system.
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, UK.
Ania
A
Stefanska
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Christopher
C
Kenyon
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Helen C
HC
Christian
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Charlotte
C
Buckley
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
Isaac
I
Shaw
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
John J
JJ
Mullins
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, UK; Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA. Electronic address: bpeault@mednet.ucla.edu.
Bruno
B
Péault
D006801:Humans; D007668:Kidney / Q000196:embryology / Q000648:ultrastructure*; D059630:Mesenchymal Stem Cells; D020286:Pericytes / Q000378:metabolism*; D061251:Primary Cell Culture; D012083:Renin / Q000378:metabolism*
D012083:Renin
CD146; NG2; mesenchymal stem cell; nephrogenesis; pericyte; renin; tissue RAS
Histol Histopathol. 1991 Apr;6(2):269-86
1802127
Hypertension. 1984 Sep-Oct;6(5):627-32
6389336
Nat Cell Biol. 2007 Mar;9(3):255-67
17293855
Nat Commun. 2011 Oct 11;2:499
21988915
Clin Exp Pharmacol Physiol. 2011 Jul;38(7):467-73
21517936
Physiol Rev. 2006 Jul;86(3):747-803
16816138
Exp Nephrol. 2001;9(3):165-70
11340300
Circ Res. 2005 Sep 16;97(6):512-23
16166562
Science. 2008 Oct 24;322(5901):583-6
18801968
Am J Pathol. 2013 Aug;183(2):542-57
23769837
Placenta. 1994 Jul;15(5):487-99
7997449
Physiol Genomics. 2011 Sep 8;43(17):1021-8
21750232
Cell Stem Cell. 2014 Feb 6;14 (2):160-73
24506883
Cell Stem Cell. 2008 Sep 11;3(3):301-13
18786417
Placenta. 2011 Dec;32(12):956-62
22018415
Am J Physiol Regul Integr Comp Physiol. 2015 Jan 15;308(2):R138-49
25427768
Stem Cells. 2015 Feb;33(2):557-73
25336400
Front Neuroendocrinol. 1998 Jul;19(3):232-52
9665837
Cytometry A. 2013 Aug;83(8):714-20
23818229
Kidney Int. 2009 Dec;76(11):1161-71
19776720
Microcirculation. 2005 Mar;12(2):151-60
15824037
Am J Pathol. 2008 Dec;173(6):1617-27
19008372
Dev Cell. 2011 Aug 16;21(2):193-215
21839917
Cell Stem Cell. 2008 Apr 10;2(4):313-9
18397751
Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1383-91
19293336
J Clin Invest. 1990 Jul;86(1):169-75
2164041
Dev Cell. 2004 May;6(5):719-28
15130496
Hypertension. 2011 Mar;57(3):532-7
21189400
Stem Cells. 2013 Feb;31(2):305-16
23165704
Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1104-9
20453168
Stem Cells Transl Med. 2012 Sep;1(9):673-84
23197874
J Am Soc Nephrol. 2009 Jun;20(6):1179-87
19470685
Am J Physiol Renal Physiol. 2014 Jan;306(2):F249-58
24226518
Physiol Rev. 2010 Apr;90(2):607-73
20393195
Front Neuroenergetics. 2010 May 21;2:null
20725515
Placenta. 1999 Jul-Aug;20(5-6):467-74
10419812
Am J Physiol Renal Physiol. 2001 Aug;281(2):F345-56
11457727
Am J Physiol. 1990 Oct;259(4 Pt 2):F660-5
2221104
Am J Pathol. 2010 Jan;176(1):85-97
20008127
J Cell Biol. 1985 May;100(5):1387-95
3886666
Annu Rev Pharmacol Toxicol. 2010;50:439-65
20055710
Anat Rec. 1979 Jan;193(1):71-97
104638
J Am Soc Nephrol. 2011 Dec;22(12 ):2213-25
22034642
Neuro Oncol. 2005 Oct;7(4):452-64
16212810
Stem Cells Dev. 2011 Mar;20(3):451-63
20923371
Cell Mol Life Sci. 2014 Apr;71(8):1353-74
24158496
Methods Cell Biol. 2008;86:295-309
18442653
Aging (Albany NY). 2015 Jun;7(6):370-82
26081073
J Am Soc Nephrol. 2013 Feb;24(3):433-44
23393316
Stem Cells Transl Med. 2015 May;4(5):538
25926331
J Clin Invest. 2002 Jun;109(11):1417-27
12045255
J Am Soc Nephrol. 2015 Jan;26(1):48-54
24904091
J Biol Chem. 2010 Apr 16;285(16):11974-82
20118482
J Am Soc Nephrol. 2012 May;23 (5):868-83
22383695
Cardiovasc Res. 1996 Oct;32(4):687-98
8915187
Genes Dev. 1996 Jun 15;10(12):1467-78
8666231
J Am Soc Nephrol. 2013 Jul;24(8):1263-73
23744888
Hypertension. 1993 Oct;22(4):513-22
8406656
J Clin Endocrinol Metab. 1992 Sep;75(3):906-10
1517384
Am J Physiol. 1991 Jun;260(6 Pt 1):E876-82
2058664
Am J Obstet Gynecol. 1995 Mar;172(3):864-7
7892876