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Human Podocytes Express Angiopoietin 1, a Potential Regulator of Glomerular Vascular Endothelial Growth Factor

Simon C. Satchell^*, Steve J. Harper^*, John E. Tooke, Dontscho Kerjaschki, Moin A. Saleem^* and Peter W. Mathieson^*

*Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom; School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, United Kingdom; and Department of Pathology, University of Vienna-Allgemeines Krakenhaus, Vienna, Austria.

Correspondence to Dr. Simon C. Satchell, Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK. Phone: 44-11-7959-5431; Fax: 44-11-7959-5438; E-mail: s.c.satchell{at}doctors.org.uk

Abstract

ABSTRACT. Vascular endothelial growth factor (VEGF) is abundantly expressed by podocytes, but its role in glomeruli is unknown. Angiopoietins are endothelial cell growth factors that function in concert with VEGF but have not previously been observed in human glomeruli. Angiopoietin 1 (Ang1) acts via the endothelial receptor Tie2 to promote maturation and stabilization of blood vessels, resisting angiogenesis and opposing some actions of VEGF. Ang1, Ang2, Tie2, and VEGF expression in normal human renal cortex was examined with immunofluorescence and immunohistochemical analyses. High-power, multiple-color, immunofluorescence analyses and additional antibodies (specific for particular components of the glomerular filtration barrier) were used to determine the exact locations of Ang1 and Tie2 in the glomerular capillary wall. Immuno-electron-microscopic analysis of rat glomeruli was used to further localize endothelial Tie2 expression. RNA and protein extracted from human glomeruli, cultured human podocytes, and cultured human endothelial cells were analyzed for Ang1, Ang2, and Tie2 by using reverse transcription-PCR and Western blotting. Ang1 was detected in podocytes in normal glomeruli and, with VEGF, was concentrated in podocyte foot processes. Tie2 was demonstrated on glomerular capillary endothelial cells, particularly on the abluminal surface. Reverse transcription-PCR and Western blotting analyses confirmed the expression of Ang1 and Tie2 in glomeruli and of Ang1 in cultured podocytes. These findings suggest a role for Ang1 in the maintenance of the glomerular endothelium and make it a good candidate to be a regulator of the actions of VEGF on glomerular permeability, resisting angiogenesis while allowing the induction of high permeability to water and small solutes.

Vascular endothelial growth factor (VEGF) is abundantly expressed in glomeruli by podocytes (visceral glomerular epithelial cells) (1), but its functional role and the factors responsible for its regulation are poorly understood. Angiopoietins are endothelial cell-specific growth factors that function in concert with VEGF in the development and maintenance of the vascular endothelium and in the regulation of vascular permeability (2). We hypothesized that angiopoietins may have important roles in adult renal glomeruli in these respects. In systemic vessels, angiopoietin 1 (Ang1) is produced by periendothelial cells, including vascular smooth muscle cells, and acts via the endothelial cell Tie2 tyrosine kinase receptor (3). Ang1 promotes vascular development and maturation (4), and its continued expression, along with Tie2 phosphorylation, in adults suggests a role in vascular maintenance (5). Ang1 reduces endothelial permeability both in adult mice (6) and in cultured human cells (7). Ang2 is produced principally by endothelial cells and antagonizes Ang1 by competitive inhibition at the Tie2 receptor (8). In adults, Ang2 is expressed in tissues undergoing vascular remodeling, where it causes loosening of the mature vascular structure, which may be a prerequisite for new vessel growth induced by VEGF (9).

Angiopoietins have not previously been observed in mature kidneys of any species, but mRNA for Ang1 and Tie2 (10) and Ang2 transgene activation (11) have been detected in the glomerular tufts of embryonic mouse kidneys, where they are proposed to be involved in glomerular development. In adult glomeruli, Ang1 has the potential to play an ongoing role in the maintenance of the glomerular permeability barrier, by stabilizing endothelial cells and allowing them to resist the potent angiogenic stimulus provided by VEGF.

We examined the expression and distribution of angiopoietins and Tie2 in adult human glomeruli by using immunofluorescence (IF) and immunohistochemical techniques and in cultured endothelial cells and podocytes by using reverse transcription (RT)-PCR and Western blotting. We further defined endothelial expression of Tie2 by using immuno-electron-microscopic (IEM) analysis of rat glomeruli. We have demonstrated that Ang1 is expressed by podocytes and is localized to foot processes and that Tie2 is expressed by glomerular endothelial cells, particularly on the abluminal membrane.

Materials and Methods

Nephrectomy Tissue
Human renal tissue was obtained from patients undergoing nephrectomies because of polar renal tumors. Within 30 min after nephrectomy, samples of cortex from the normal pole were obtained for preparation of frozen sections and paraffin sections and for extraction of glomeruli by sieving.

Immunostaining
Frozen sections were air-dried before immunostaining with polyclonal antibodies to Ang1, Ang2, Tie2, or VEGF (Santa Cruz Biochemicals, Santa Cruz, CA). Control sections were incubated with same-species Ig or with specific antibodies that had been preincubated with blocking peptide (Santa Cruz). Secondary antibodies were FITC-labeled anti-goat IgG (for Ang1 and Ang2) or FITC-labeled anti-rabbit IgG (for Tie2 and VEGF). Formalin-fixed paraffin sections were stained with the nitro-blue tetrazolium method, as previously described (12), using the same antibodies. The exact localization of angiopoietins and Tie2 within glomeruli was determined by high-power, multiple-color, IF analysis (at a magnification of x1000, with oil immersion), using monoclonal antibodies specific for particular components of the glomerular filtration barrier, i.e., platelet-endothelial cell adhesion molecule-1 (R&D Systems, Minneapolis, MN) for endothelial cells, type IV collagen 3 chain (Wieslab AB, Lund, Sweden) for the glomerular basement membrane, and nephrin (a gift from Karl Tryggvason, Karolinska Institute, Stockholm, Sweden) for podocyte foot processes. Anti-mouse IgG secondary antibodies were labeled with FITC, tetrarhodamine isothiocyanate, or aminomethylcoumann acetic acid.

IEM
Blocks of renal cortex from perfusion-fixed (4% paraformaldehyde in phosphate buffer, pH 7.2) rat kidneys were dehydrated in ethanol and embedded in K4M Lowicryl (Polysciences Inc., Warrington, PA) (13). Ultrathin sections were incubated with antibodies to Tie2 (as described above), followed by goat anti-rabbit IgG-gold (10 nm) conjugate. In control sections, primary antibodies were omitted or replaced by irrelevant antibodies. Sections were stained with lead citrate and examined with a JEOL 1010 electron microscope (JEOL, Tokyo, Japan). Rat kidney sections were also immunostained for Tie2 as described above for human kidneys, to confirm similar Tie2 distributions.

Cell Culture
Human microvascular endothelial cells (HMVEC) (derived from adult lung tissue; Clonetics Corp., San Diego, CA) were obtained at passage 3 and used for experiments up to passage 7. A conditionally immortalized human podocyte cell line was cultured as described previously (14).

RT-PCR
RNA was extracted from sieved glomeruli and from cultured cells by using a standard phenol-chloroform method and was reverse-transcribed with a kit (Promega, Madison, WI) before PCR amplification of sequences specific for Ang1, Ang2, and Tie2 (Table 1). The identity of the PCR products was confirmed by forward and reverse sequence analysis (ABI Prism 377; ABI, Madison, WI).

Results

Ang1 was detected in a linear pattern in adult glomeruli in frozen and paraffin-embedded sections (Figures 1 and 2), but Ang2 was not detected. Ang1 was also detected in vascular smooth muscle cells, as in other tissues (3). Tie2 was detected in a predominantly endothelial distribution in glomeruli (Figure 3). Using high-power, multiple-color, IF analyses, we demonstrated that Ang1 was localized externally to the glomerular basement membrane in the capillary wall and that its distribution was identical to that of nephrin, confirming its expression in podocyte foot processes (Figure 4, A to C, G, and H). VEGF was distributed in a similar pattern (Figure 4D), whereas Tie2 was expressed on the glomerular endothelium (Figure 4, E to H). As assessed in IEM analyses of normal rat glomeruli, Tie2 was expressed on both surfaces of the endothelium but predominantly on the abluminal surface (Figure 5). Some Tie2 was also detected on podocyte foot processes.

View larger version (115K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 1. Immunofluorescence (IF) staining of consecutive fresh-frozen sections of normal cortex. Magnification, x400. (A) Glomeruli stain positively for angiopoietin 1 (Ang1). (B) Glomeruli are negative for Ang2.

View larger version (71K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 3. IF staining of normal cortex for Tie2. (A and B) Consecutive sections are presented. Magnification, x200. (A) Tie2 is detected in glomeruli. (B) The control antibody-treated section does not exhibit glomerular staining. (C) Tie2 is distributed in a capillary endothelial pattern (arrows). Magnification, x1000.

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 4. Multiple-color, high-power, IF analysis of sections through individual glomerular capillary loops, stained with various antibodies. b, Bowman’s space; c, capillary lumen. Magnification, x1000. (A) Ang1 (green) is external to endothelial platelet-endothelial cell adhesion molecule-1 (red). (B) Ang1 (green) is also external to type IV collagen (red) in the glomerular basement membrane. (C) Ang1 (green) colocalizes with nephrin (red) in the same layer of the glomerular capillary wall (arrow), confirming expression of Ang1 in podocyte foot processes. (D) Vascular endothelial growth factor (VEGF) (green) is similarly distributed in podocyte foot processes, external to endothelial platelet-endothelial cell adhesion molecule-1 (red). (E and F) Tie2 (green) is expressed on the endothelium, internal to podocyte foot processes, which are labeled for nephrin (red) (E), and internal to the glomerular basement membrane (red) (F). (G and H) Ang1 (green) in podocyte foot processes is external to the glomerular basement membrane (blue), whereas endothelial Tie2 (red) is internal.

View larger version (62K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 5. Antibody staining for Tie2 in normal rat glomeruli. b, Bowman’s space; c, capillary lumen. (A, inset) Tie2 was localized in normal rat glomeruli by IF analysis. Tie2 is located in the peripheral capillary loops, as in human glomeruli. Magnification, x700. (A) As assessed by immunogold electron microscopy, Tie2 (arrows) is primarily located on the cell membranes of endothelial cells that face the glomerular basement membrane (gbm), as particularly well resolved in this grazing section through a glomerular capillary loop, displaying the pores of the endothelium (e). In addition, Tie2 is also observed on the cell membranes of podocytes. Magnification, x35,000. (B) An additional immuno-electron micrograph demonstrates expression of Tie2 (arrowheads) on a glomerular endothelial cell and, in particular, on the cell membrane attached to the glomerular basement membrane. Magnification, x25,000.

View larger version (126K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 2. Immunohistochemical analysis of paraffin sections of normal cortex. Magnification, x400. (A) Glomeruli and vascular smooth muscle cells are positive for Ang1. (B) Staining for Ang1 is lost after preincubation of antibody with blocking peptide.

View larger version (66K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 6. Reverse transcription (RT)-PCR analyses of Ang1, Ang2, Tie2, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), using mRNA extracted from human microvascular endothelial cells (HMVEC), glomeruli, and a conditionally immortalized human podocyte cell line. Ang1 mRNA is present in podocytes and total glomeruli and is present at lower levels in HMVEC. Ang2 mRNA is present in HMVEC but is barely detectable in glomeruli and is absent from podocytes. Tie2 mRNA is present in HMVEC and glomeruli but is absent from podocytes. RT-PCR analysis of GAPDH confirms the addition of equal amounts of cDNA template.

View larger version (41K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 7. Western blotting analyses of Ang1, Ang2, and Tie2, using protein extracted from HMVEC, glomeruli, and a conditionally immortalized human podocyte cell line. Images were derived from identical gels loaded with the same amount (20 µg) of the same protein extract samples. Recombinant Ang1 and Ang2 (100 ng each) were used as positive control samples for the Ang1- and Ang2-stained membranes, respectively. Ang1 is expressed in HMVEC, glomeruli, and podocytes. Ang2 is expressed in HMVEC only, and Tie2 is expressed in glomeruli and HMVEC but not podocytes. Actin bands confirm the loading of comparable amounts of extracted protein.

We have demonstrated that Ang1 is expressed by podocytes both in culture and in mature human glomeruli. This is an important development based on previous reports of the detection of Ang1 mRNA in embryonic mouse glomerular tufts (10) and is consistent with the production of Ang1 by periendothelial cells in other tissues (3). Furthermore, Ang1 seems to be concentrated in podocyte foot processes in vivo, as is VEGF. Taken together with the presence of Tie2 (described here) and VEGF receptor 2 (16) on glomerular endothelium, these findings have implications for the functional roles of these molecules in the regulation and maintenance of the glomerular endothelium. The transport of Ang1 and VEGF within podocytes to the foot processes suggests that these molecules are released to have some local action, most obviously on the adjacent endothelium.

The known actions of Ang1 that may be important in glomeruli include stabilization of capillary structure, promotion of endothelial cell survival, and reduction of endothelial permeability. Ang1 reduces permeability via the paracellular route, by increasing the integrity of interendothelial cell junctions (4,7). This action of Ang1 may at first appear inconsistent with the high permeability to water and small molecules exhibited by the glomerular endothelium. However, this high permeability is largely attributable to extensive transcellular endothelial fenestrations, which may be induced by VEGF produced by podocytes. This juxtaposition is analogous to that in other tissues, such as the choroid plexus, where endothelial fenestrations are induced by VEGF produced by the underlying epithelium (17). Ang1 may stabilize the capillary structure while allowing VEGF to promote high permeability to water and small molecules. The presence of Ang1 helps explain why high concentrations of glomerular VEGF in adults do not cause angiogenesis in the glomerular capillaries.

The IEM data indicating Tie2 expression predominantly on the abluminal surface of the glomerular endothelium are the first to differentiate between luminal and abluminal growth factor receptor expression in these cells. These findings are consistent with our hypothesis that Ang1 from podocytes acts on glomerular endothelial cells, and they are analogous to findings of VEGF receptor 2 expression on the abluminal surface of other endothelia (16). The detection of Tie2 on rat podocytes suggests that there may also be an autocrine loop.

The failure to detect Ang2 protein in normal adult glomeruli is consistent with previous observations in embryonic mice (11) and in human subjects, where Ang2 is readily detected only in tissues undergoing active vascular remodeling or repair (8). However, Ang2 is likely to be important in the endothelial response to glomerular injury. Both Ang1 and Ang2 were detected in cultured endothelial cells (in addition to Tie2), although there was no evidence of their expression in glomerular endothelial cells in vivo. This is consistent with previous reports indicating that, whereas endothelial cells may produce angiopoietins when stressed by injury or culture, they do not usually do so in stable tissue (3,8).

Dysregulation of angiopoietins may be important in glomerular disease (as has been demonstrated for VEGF) (18) and may provide a therapeutic target in diseases associated with increased glomerular permeability or glomerular capillary damage. In animal models, exogenous VEGF has been demonstrated to augment glomerular repair (19) but optimal results may be produced with the combination of Ang1 and VEGF (20).

Acknowledgments

Dr. Satchell was supported by a National Health Service South West Research and Development Executive Grant. Dr. Harper was supported by Wellcome Trust Grant 057936/99. Prof. Kerjaschki was supported by Fonds zur Foerderung der Wissenschaftlichen Forschung, Sonderforschungsbereich 005, Project 007. We thank Regeneron Pharmaceuticals Inc. (Tarrytown, NY) for providing Ang1 and K. Tryggvason (Karolinska Institute) for providing the nephrin-specific antibody.

References

1. Brown LF, Berse B, Tognazzi K, Manseau EJ, Van de Water L, Senger DR, Dvorak HF, Rosen S: Vascular permeability factor mRNA and protein expression in human kidney. Kidney Int 42: 1457–1461, 1992[Medline]
2. Peters KG: Vascular endothelial growth factor and the angiopoietins: Working together to build a better blood vessel. Circ Res 83: 342–343, 1998[Free Full Text]
3. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD: Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87: 1161–1169, 1996[CrossRef][Medline]
4. Papapetropoulos A, Garcia-Cardena G, Dengler TJ, Maisonpierre PC, Yancopoulos GD, Sessa WC: Direct actions of angiopoietin-1 on human endothelium: Evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest 79: 213–223, 1999[Medline]
5. Wong AL, Haroon ZA, Werner S, Dewhirst MW, Greenberg CS, Peters KG: Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues. Circ Res 81: 567–574, 1997[Abstract/Free Full Text]
6. Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD: Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6: 460–463, 2000[CrossRef][Medline]
7. Gamble JR, Drew J, Trezise L, Underwood A, Parsons M, Kasminkas L, Rudge J, Yancopoulos G, Vadas MA: Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions. Circ Res 87: 603–607, 2000[Abstract/Free Full Text]
8. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science (Washington DC) 277: 55–60, 1997[Abstract/Free Full Text]
9. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegand SJ: Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science (Washington DC) 284: 1994–1998, 1999[Abstract/Free Full Text]
10. Yuan HT, Suri C, Yancopoulos GD, Woolf AS: Expression of angiopoietin-1, angiopoietin-2, and the Tie-2 receptor tyrosine kinase during mouse kidney maturation. J Am Soc Nephrol 10: 1722–1736, 1999[Abstract/Free Full Text]
11. Yuan HT, Suri C, Landon DN, Yancopoulos GD, Woolf AS: Angiopoietin-2 is a site-specific factor in differentiation of mouse renal vasculature. J Am Soc Nephrol 11: 1055–1066, 2000[Abstract/Free Full Text]
12. Bailey E, Bottomley MJ, Westwell S, Pringle JH, Furness PN, Feehally J, Brenchley PE, Harper SJ: Vascular endothelial growth factor mRNA expression in minimal change, membranous, and diabetic nephropathy demonstrated by non-isotopic in situ hybridisation. J Clin Pathol (Lond) 52: 735–738, 1999[Abstract]
13. Armbruster BL, Carlemalm E, Chiovetti R, Garavito RM, Hobot JA, Kellenberger E, Villiger W: Specimen preparation for electron microscopy using low temperature embedding resins. J Microsc (Oxf) 126: 77–85, 1982[Medline]
14. Saleem M, Reiser J, Mundel P: A conditionally immortalized human podocyte cell line which inducibly expresses markers of growth arrest and differentiation [Abstract]. J Am Soc Nephrol 10: 560A, 1999
15. Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U, Risau W: Angiopoietin-1 induces sprouting angiogenesis in vitro. Curr Biol 8: 529–532, 1998[CrossRef][Medline]
16. Feng D, Nagy JA, Brekken RA, Pettersson A, Manseau EJ, Pyne K, Mulligan R, Thorpe PE, Dvorak HF, Dvorak AM: Ultrastructural localization of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) receptor-2 (FLK-1, KDR) in normal mouse kidney and in the hyperpermeable vessels induced by VPF/VEGF-expressing tumors and adenoviral vectors. J Histochem Cytochem 48: 545–556, 2000[Abstract/Free Full Text]
17. Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W: Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140: 947–959, 1998[Abstract/Free Full Text]
18. de Vriese AS, Tilton RG, Elger M, Stephan CC, Kriz W, Lameire NH: Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol 12: 993–1000, 2001[Abstract/Free Full Text]
19. Kim YG, Suga SI, Kang DH, Jefferson JA, Mazzali M, Gordon KL, Matsui K, Breiteneder-Geleff S, Shankland SJ, Hughes J, Kerjaschki D, Schreiner GF, Johnson RJ: Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy. Kidney Int 58: 2390–2399, 2000[CrossRef][Medline]
20. Chae JK, Kim I, Lim ST, Chung MJ, Kim WH, Kim HG, Ko JK, Koh GY: Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization. Arterioscler Thromb Vasc Biol 20: 2573–2578, 2000[Abstract/Free Full Text]

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