Journal Information
Vol. 16. Issue. S3.June 1996
Pages 1-58
Share
Share
Download PDF
More article options
Vol. 16. Issue. S3.June 1996
Pages 1-58
Full text access
Fisiología y fisiopatología de las células mesangiales
Visits
2401
P. MENÉ
This item has received
2401
Visits
Article information
Full Text
NEFROLOGIA. Vol. XVI. Suplemento 3. 1996 Physiology and pathophysiology of the mesangial cell P. Menè Cattedra di Nefrologia, Università degli Studi. «La Sapienza» di Roma The intercapillary area of the kidney glomerulus w a s first described and named «mesangium» by Zimmermann in 1933 1. The advent of electron microscopy enabled Marinozzi in Italy 2 a n d Latta in the U.S. 3 to conclusively demonstrate that a separate cell type exists in the kidney glomerulus, in add i t i o n to epithelial and endothelial cells lining a r o u n d the basement membrane. The functions of t h e s e «mesangial» cells have been subsequently elucidated, based on recognition of their contractil e phenotype and involvement in a variety of glomerular diseases (table I) 4-7. Mechanical / structural functions M e s a n g i a l cells are relatively rare in a normal g l o m e r u l u s , not exceeding 2-3 nuclei in a typical l i g h t microscopy section of a mesangial space. T h e i r total number is approximately 250-300 in a r a t glomerulus 8 . Scarce extracellular matrix surrounds mesangial cells and bridges the space betw e e n neighbouring podocytes and endothelial cells. A direct relationship exists with the glomerul a r basement membrane at specialized structures t e r m e d «mesangial angles» by Kriz and Sakai 9 . These links may serve a mechanical function, exert i n g traction on the basement membrane so to c o u n t e r b a l a n c e the hydraulic force driving ultrafiltration 10. T h e smooth muscle phenotype in vivo, and the ability of cultured mesangial cells to undergo contraction when exposed to vasonstrictors, and relax i n response to vasodilators, has attracted interest around the possibility that these cells may regulate the caliber of glomerular capillaries, and thus bloo d pressure and flow, with obvious implications o n ultrafiltration 4 - 7 , 1 1 . While conclusive in vivo evidence is difficult to achieve, many ex vivo or in vitro findings suggest that this may well be the case. First, the volume of glomeruli varies in response to contractile agents, indicating that responsive s m o o t h muscle elements reside within the capil l a r y tuft 4 - 1 0 . As mesangial cells are abundantly endowed with actin and myosin bundles, they are m a j o r candidates for this mechanical function. A d d i t i o n a l l y , contractility in culture, regulated by a variety of vasoactive agents 5 , is consistent with such model. Second, the single nephron glomerular filtration rate is a function of two determinants: t h e mean net ultrafiltration pressure, resulting f r o m the balance between hydraulic and oncotic p r e s s u r e s across the filtering unit, and the ultrafiltration coefficient, Kf. This parameter has been ex- Table I. Recognized functions of glomerular mesangial cells 1. Mechanical - structural -- Perivascular, intercapillary cell (pericyte) -- GBM tensioning, countering Puf -- Contraction / regulation of filtration surface area -- Matrix elaboration, processing -- Reparative proliferation following immune injury 2. Ultrafiltration -- GBM-like filtration of plasma -- Sieving of macromolecules, immune complexes 3. Immune-effector cell -- Antigen presenting -- Phagocytosis -- Reactive oxygen species production / scavenging -- Leukocyte chemoattraction 4. Biosynthesis -- Bioactive lipids -- Enzymes -- Matrix components -- Cytokines -- Growth factors -- Adhesion molecules Correspondence to: Paolo Menè, M.D. Cattedra di Nefrologia 2.ª Clinica Medica Policlinico Umberto I Viale del Policlinico 00161 Roma Italy 8 MESANGIAL CELL PATHOPHYSIOLOGY perimentally found to vary in several pathophysiol o g i c settings. Interestingly, both its determinants, the surface area (A) of capillaries and the effective h y d r a u l i c permeability of the glomerular capillary w a l l (k), are likely to change as the result of mes a n g i a l contraction 1 2 . Third, selective experiment a l mesangial injury by specific antisera often res u l t s in impairment of glomerular flow and f i l t r a t i o n , that would be difficult to explain if mesangial cells had no role in glomerular hemodynamics 5, 6, 11. Contraction is not the only mechanical function subserved by mesangial cells. Deposition of extracellular matrix is another prominent feature with likely implications for glomerular function. Not only does matrix contribute to the normal architecture of the mesangial space, but it also constitutes a tridimensional meshwork that allows filtration of blood, s i m i l a r to the glomerular basement membrane (GBM) 4-7. As a matter of fact, the biochemical comp o s i t i o n of the mesangial matrix resembles that of the GBM, while its spatial organization seems bett e r suited to trapping of macromolecules and imm u n e complexes, which are then disposed of thr o u g h phagocytosis and subsequent progression across the mesangial space 13. U p r e g u l a t i o n of mesangial matrix is an interest i n g feature of several glomerular diseases. This event may result from increased deposition of matrix, reduced catabolism, or possibly the combination of both 14. A number of growth factors and cyt o k i n e s , both released by glomerular cells and infiltrating leukocytes, appear well suited to stimul a t e matrix accumulation. This event seems to underlie glomerular lesions in slow-progressing, noninflammatory conditions, such as diabetes or focal g l o m e r u l o s c l e r o s i s . The occurrence of mesangial h y p e r p l a s i a , or proliferation of the cells, whose number is actually increased, is often encountered i n more rapidly evolving diseases, with extensive l e u k o c y t e infiltration, necrotizinglesions, and the signs of acute or subacute inflammation. These are features of mesangiocapillary nephritis, lupus nephritis, rapidly progressive glomerulonephritis, or vasculitis. Clearly, the pathophysiologic mechanism of m e s a n g i a l involvement is different, although the common denominator seems represented by in situ cell «activation» with phenotypic changes. This has brought interest into the functional connotations of m e s a n g i a l cells, which appear rather poorly differ e n t i a t e d under resting conditions in the normal kidney. Latta coined the expression «myofibroblast» to describe this wide potential of mesangial cells to express a contractile or secretory / reparative phen o t y p e , according to the functional needs and the presence of appropriate stimuli 4, 11. Indeed, recent evidence that smooth muscle actin isoforms are exp r e s s e d by mesangial cells upon induction of immune-mediated damage points to the availability of «markers» of mesangial activation in vivo 11 . Immunologic functions T h e presence of specialized phagocytes within the glomerular mesangium has long been a matter of controversy. The mesangial population is mostly a c c o u n t e d for by a smooth muscle / fibroblastic p h e n o t y p e that seems only marginally suited for i m m u n e functions as either antigen-presenting c e l l s or «professional» phagocytes 4 - 7 . Only 2 to 5 % of the cells confined in mesangial areas display o b v i o u s markers of bone marrow origin, such as the leukocyte common antigen or the Ia marker of p h a g o c y t i c differentiation 1 5 , 16 . Interestingly, bone marrow suppressive treatment rapidly depletes the glomerulus of these cells, clearly showing that they Fig. 1.--Binding of undifferentiated human myelomonocytes of the U-937 cell line to cultured human mesangial cells. Note tight a d h e s i o n of monocytes to underlying mesangial cells via cytoplasmic processes. Scanning electron microscopy, original magnification 1000 ×. 9 P. MENE migrate into the mesangium from the blood stream a n d differentiate in situ, most likely to serve phagocytic functions 16. Culture of glomerular explants g i v e s rise to a homogeneous cell population devoid of such markers, that should be considered as «intrinsic» mesangial cells. Nevertheless, evidence h a s been gathered showing that these cultures indeed internalize and process opsonized gold partic l e s , latex-coated microbeads, and immune comp l e x e s 1 7 . The process appears to involve Fc r e c e p t o r s , whose cross-linking appears to elicit specific biochemical events such as phosphoinosit i d e breakdown, changes of free cytosolic Ca 2 + ( [ C a2 + ] i ) , and prostaglandin (PG) biosynthesis 1 8 , 19. The release and scavenging of reactive oxygen spec i e s , not only as a byproduct of normal cellular metabolism, but also in response to specific immunologic challenge, further points to an active partic i p a t i o n in the immune response 2 0 . This may acc o u n t for the accumulation of immune complexes in mesangial areas occurring in various experiment a l and human nephritides, as a result of trapping through the reticular structure of the mesangial mat r i x , and delayed or insufficient clearance of the deposits 21. Failure of the mesangium to rapidly disp o s e of the material accumulated during filtration or formed in situ may explain this common finding, probably responsible for triggering subsequent glomerular inflammation and leukocyte chemoattraction 21. R e c e n t work has elucidated the mechanisms by which mesangial cells represent a target for neutrophils or monocytes / macrophages that infiltrate the glomerulus 22, 23. Mesangial cells express a variety of integrins and adhesion molecules that promote leuk o c y t e chemoattraction and adhesion (figure 1). W h i l e devoid of endothelial integrins such as ELAM-1, mesangial cells express intercellular adhes i o n molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), RANTES and monocyte chemoattractant protein-1 (MCP-1), all of which app e a r upregulated by several cytokines and ligands r e l e a s e d at the site of inflammation 2 3 - 2 8 . Together with matrix components that bind leukocyte counterreceptors, this sets the stage for further leukocyte i n f i l t r a t i o n and local activation, thus perpetuating glomerular inflammation 22. The role of vasoactive agents such as constrictor prostaglandins (PG), leuk o t r i e n e s (LT), platelet activating factor (PAF) and e v e n the endothelial products endothelin-1 (ET-1) and angiotensin II (ANG II) remains to be elucidat e d . As discussed earlier, these compounds may m o d i f y the mesangial phenotype and promote expression of surface determinants that trigger homing of leukocytes and amplify local damage. Local hem o d y n a m i c s itself, controlled by such vasoactive 10 a g e n t s , may indeed be relevant to glomerular inflammation. Biosynthetic functions M e s a n g i a l cells have secretory features beyond b i o s y n t h e s i s and layering of extracellular matrix. Both in vitro and in vivo, there is extensive evidence that bioactive lipids, such as arachidonate metab o l i t e s or PAF, enzymes, vasoactive peptides, and c y t o k i n e s are locally produced and released. I n t e r e s t i n g l y , mesangial cells generally express receptors for all of these compounds, pointing to autocrine effects or paracrine interactions with contig u o u s mesangial cells, glomerular epithelial and endothelial cells, and possibly infiltrating leukocyt e s during glomerular inflammation. Table II lists t h e major products of mesangial cells presently identified. Bioactive lipids are generally labile derivatives of p l a s m a membrane turnover, released as means of i n t e r c e l l u l a r communication upon stimulation of m e m b r a n e - a s s o c i a t e d phospholipases. Endowed with powerful vasomotor activity, PG, LT and PAF h a v e other cellular actions that include regulation o f proliferation and protein synthesis, leukocyte chemoattraction, and probably vascular permeability 29. Table II. M a j o r products of glomerular mesangial cells Growth factors Platelet-derived growth factor Transforming growth factor - ß1 Insulinlike growth factor 1 Cytokines Interleukins 1, 6, 8 Tumor necrosis factor GM - colony stimulating factor Adhesion molecules, chemokines ICAM-1 VCAM-l MCP-1 RANTES Bioactive lipids Prostaglandins, leukotrienes, lipoxins Platelet activating factor Vasoactive agents Endothelin-1 Nitric oxide (EDRF) Enzymes Renin Neutral proteinases MESANGIAL CELL PATHOPHYSIOLOGY Renin has been one of the first enzymes identif i e d in mesangial cultures 3 0 , 31 . The patterns of ren i n regulation match those described for juxtaglom e r u l a r cells, suggesting structural similarities b e t w e e n cell populations that may be electromec h a n i c a l l y coupled via a syncytial organization 3 2 . I n t e r e s t i n g l y , cultured cells retain this ability to f o r m syncytial structures, that have been recently e x p l o i t e d by means of diffusible tracers and microinjection 33. T h e significance of renin biosynthesis may be better appreciated if one realizes that components of the renin-angiotensin system, including convert i n g enzyme activity in glomerular endothelial cells, may locally function to generate active ANG I I in situ, within the glomerular microcirculation. Since abundant receptors exist for this peptide both i n mesangial cells, afferent and efferent arterioles, a s well as glomerular epi- thelial cells, ANG II is well suited for autocrine or paracrine regulation of l o c a l hemodynamics, along with cell growth and matrix formation 5, 6, 12, 34. Another peptide relevant to the control of vascular tone, ET-1, has been recently identified as a product of mesangial cells 35, 36. Similar to the renin-angiotensin system, it is likely that local loops link the b i o s y n t h e s i s of ET-1 by mesangial and neighbour i n g endothelial cells to mesangial receptors, with implications for a wide range of pathophysiological e v e n t s . Both populations also exhibit nitric oxide synthetase activity 37, 38. As the constitutive and inducible isoforms of this enzyme release the potent vasodilator, nitric oxide, or endothelial-derived relaxing factor (EDRF), an endothelial - smooth muscle feedback has been proposed, with two opposite branches regulating the vascular tone of the glomerular capillary microcirculation. C y t o k i n e s are another relevant product of mesangial cells. Several interleukins, notably IL-1 and IL-6, are produced by «activated» cells, and act on r e c e p t o r s expressed by the same cells 3 9 - 4 2 . Interferon, GM-CSF, tumor necrosis factor, MCP-1, R A N T E S 2 6 , 27, 43, 44 a r e other examples of the wide host of mesangial peptides acting on bone marrowderived cells that also appear to mediate paracrine i n t e r a c t i o n s within the inflammed glomerulus. A d h e s i o n molecules belonging to the integrin superfamily regulate adhesion and cell-to-cell immun e reactions 2 2 . Platelet-derived growth factor (PDGF) isoform AA is the predominant growth factor produced by mesangial cells 45, 46 , although relevant levels of transforming growth factor-1 (TGFß) 47, insulinlike growth factor 1 (IGF-l) 48, fibroblast growth factor (FGF), epidermal growth factor (EGF) 46 h a v e been reported. Interestingly, PDGF gene expression appears an early step in the response of mesangial cells to several mitogens, such as thrombin, ET-1, etc. 49. The biological significance of this r e p o n s e is unclear, as mesangial cells express mostly ß isoforms of the receptor for PDGF, which are known to bind the homodimer BB or the heter o d i m e r AB, but not the endogenous form AA 4 9 . The endogenous peptide is thus likely to act at sites o t h e r than the intrinsic mesangial cells, since its r o l e in the early phase of mesangial proliferative g l o m e r u l o n e p h r i t i d e s has been convincingly s h o w n 5 0 . A vast body of studies employing blocking anti-TGF-ß1 antibodies or binding glycans imp l i c a t e s also this growth factor in a variety of glom e r u l a r diseases with predominant mesangial expression 51-53. A unifying view combines the two growth factors as sequential activators and regulat o r s of mesangial proliferation and matrix deposition 11. Conclusions T h e vast number of publications focusing on mesangial cells testifies to the extreme interest rais e d in recent years by this apparently amorphous a n d inert structure of the glomerulus. The search f o r a key player in the reshaping of the filtering u n i t that occurs following immunologic or metabolic insult, has placed high hopes on the possibil i t y of understanding and manipulating mesangial c e l l function. It is unclear whether these expectat i o n s will be eventually met, introducing pharmac o l o g i c means to arrest the relentless progression o f glomerular scarring that characterizes so many r e n a l diseases. In any circumstance, the contribut i o n of cell culture and molecular biology will be c e r t a i n l y acknowledged as a major effort in the understanding of renal function in health and disease. References 1. Z i m m e r m a n n KW: Über den Bau des Glomerulus der menschlichen Niere. Weittere Mitteilungen. Z Mikrosk Anat Forsch 32:176-278, 1933. 2. M a r i n o z z i V: Struttura ed istofisiologia del glomerulo. Atti d e l II Corso di Aggiornamento professionale, Nefrologia Moderna. Rome, pp. 33-51, 1961. 3. Latta H, Maunsbach AB y Madden SC: The centrolobular reg i o n of the renal glomerulus studied by electron microscopy. J Ultrastruct Res 4:455-472, 1960. 4. L a t t a H: An approach to the structure and function of the glomerular mesangium. J Am Soc Nephrol 2:S65-S73, 1992. 5. Menè P, Simonson MS y Dunn MJ: Physiology of the mesangial cell. Physiol Rev 69:1347-1424, 1989. 6. Schlondorff D: The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J 1:272-281, 1987. 7. Davies M: The mesangial cells: a tissue culture view. Kidney Int 45:320-327, 1994. 11 P. MENE 8. Olivetti G, Anversa P, Melissari M y Loud A: Morphometry o f the renal corpuscle during post-natal growth and compensatory hypertrophy. Kidney Int 17:438-454, 1980. 9. S a k a i T y Kriz W: The structural relationship between mesangial cells and basement membrane of the renal glomerulus. Anat Embryol 176:373-386, 1987. 10. Kriz W, Elger M, Lemley KV y Sakai T: Mesangial cell-glom e r u l a r basement membrane connections counteract glomerular capillary and mesangium expansion. Am J Nephrol 10 (suppl 1):4-13, 1990. 11. J o h n s o n RJ, Floege J, Yoshimura A, Iida H, Couser WG y Alpers CE: The activated mesangial cell: a glomerular «myofibroblast»? J Am Soc Nephrol 2:S190-S197, 1992. 12. B r e n n e r BM, Dworkin LD y Ichikawa I: Glomerular ultrafiltration, in: Brenner BM, Rector FC, Jr. (eds). The Kidney, 3rd edition. WB Saunders, pp. 124-144, 1986. 13. L a t t a H y Fliegel S: Mesangial fenestrations, sieving, filtration, and flow. Lab Invest 52:591-598, 1985. 14. C o u c h m a n JR, Beavan LA y McCarthy KJ: Glomerular mat r i x : synthesis, turnover and role in mesangial expansion. Kidney Int 45:328-335, 1994. 15. Schreiner GF: The mesangial phagocyte and its regulation of contractile cell biology. J Am Soc Nephrol 2:S74-S82, 1992. 16. Schreiner GF y Unanue ER: The origin of the rat mesangial phagocyte and its expression of the leukocyte common antigen. Lab Invest 51:515-523, 1984. 17. S i n g h a l PC, Gupta S, Shen Z y Schlondorff D: Effects of P G E 2 a n d a thromboxane A 2 a n a l o g u e on uptake of IgG c o m p l e x e s and LDL by mesangial cells. Am J Physiol 261:F537-F544, 1991. 18. Hora K, Satriano JA, Santiago A, Mori T, Stanley ER, Shan Z y Schlondorff D: Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide-1 and colony stim u l a t i n g factor-1. Proc Natl Acad Sci USA 8 9 : 1 7 4 5 - 1 7 4 9 , 1992. 19. K n a u s s TC, Menè P, Ricanati SA, Kester M, Dubyak GR, Emancipator SN y Sedor JR: Immune complex activation of rat glomerular mesangial cells: dependence on the Fc region of antibody. Am J Physiol 257:F478-F485, 1989. 20. B a u d L, Fouqueray B, Philippe C y Ardaillou R: Reactive oxygen species as glomerular autacoids. J Am Soc Nephrol 2:S132-S138, 1992. 21. Couser WG: Mediation of immune glomerular injury. J Am Soc Nephrol 1:13-29, 1990. 22. W u t r i c h RP: Intercellular adhesion molecules and the kidney. J Am Soc Nephrol 3:1201-1211, 1992. 23. M e n è P, Fais S, Cinotti GA, Pugliese F, Luttmann W y Thierauch K-H: Regulation of U-937 monocyte adhesion to cultured human mesangial cells by cytokines and vasoactive agents. Nephrol Dial Transplant 10:481-489, 1995. 24. B r a d y HR, Denton MD, Jiménez W, Takata S, Palliser D y Brenner BM: Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury. Kidney Int 42:480487, 1992. 25. D e n t o n MD, Marsden PA, Luscinskas FW, Brenner BM y Brady HR: Cytokine-induced phagocyte adhesion to human mesangial cells: role of CD11/CD18 integrins and ICAM-1. Am J Physiol 261:F1071-F1079, 1991. 26. Rovin BH y Tan LC: Role of protein kinase pathways in IL-1i n d u c e d chemoattractant expression by human mesangial cells. Kidney Int 46:1059-1068, 1994. 27. Wolf G, Aberle S, Thaiss F, Nelson PJ, Krensky AM, Neilson EG y Stahl RAK: TNF induces expression of the chemoatt r a c t a n t cytokine RANTES in cultured mouse mesangial cells. Kidney Int 44:795-804, 1993. 28. B r e n n a n DC, Jevnikar AM, Takei F y Reubin-Kelley VE: Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1. Kidney Int 38:1039-1046, 1990. 29. D u n n MJ: Renal prostaglandins, in: Dunn MJ (ed). Renal Endocrinology. Williams & Wilkins, pp. 1-74, 1983. 30. C h a n s e l D, Dussaule J-C, Ardaillou N y Ardaillou R: Identification and regulation of renin in cultured human mesangial cells. Am J Physiol 252:F32-F38, 1987. 31. Pfeilschifter J, Kurtz A y Bauer C: Inhibition of renin secret i o n by platelet activating factor (acetylglyceryl ether p h o s p h o r y l c h o l i n e ) in cultured rat renal juxtaglomerular cells. Biochem Biophys Res Commun 127:903-910, 1985. 32. Frank M y Kriz W: Scanning electron microscopy studies of the vascular pole of the rat glomerulus. Anat Rec 204:149152, 1982. 33. Iijima K, Moore LC y Goligorsky MS: Syncytial organization o f cultured rat mesangial cells. Am J Physiol 2 6 0 : F 8 4 8 F855, 1991. 34. J a r d i n e AG: Angiotensin II and glomerulonephritis. J Hypertens 13:487-493, 1995. 35. Zoja C, Orisio S, Perico N, Benigni A, Morigi M, Benatti L, Rambaldi A y Remuzzi G: Constitutive expression of endothelin gene in cultured human mesangial cells and its modulation by transforming growth factor ß, thrombin, and a thromboxane analogue, Lab Invest 64:16-25, 1991. 36. Perico N y Remuzzi G: Role of endothelin in glomerular injury. Kidney Int 43:S76-S80, 1993. 37. S h u l t z PJ, Tayeh MA, Marletta MA y Raij L: Synthesis and action of nitric oxide in rat glomerular mesangial cells. Am J Physiol 261:F600-F606, 1991. 38. P f e i l s c h i f t e r J, Rob P, Mulsch A, Fandrey J, Vosbeck K y Busse R: Interleukin 1ß and tumour necrosis factor a induce a macrophage-type of nitric oxide synthase in rat renal mesangial cells. Eur J Biochem 203:251-255, 1992. 39. L o v e t t DH, Martin M, Bursten S, Szamel M, Gemsa D y R e s c h K: Interleukin 1 and the glomerular mesangium. III. IL-1-dependent stimulation of mesangial cell protein kinase activity. Kidney Int 34:26-35, 1988. 40. Werber HI, Emancipator SN, Tykocinski ML y Sedor JR: The interleukin 1 gene is expressed by rat glomerular mesangial cells and is augmented in immune complex glomerulonephritis. J Immunol 138:3207-3212, 1987. 41. I k e d a M, Ikeda U, Ohara T, Kusano E y Kano S: Recombinant interleukin-6 inhibits the growth of rat mesangial cells in culture. Am J Pathol 141:327-334, 1992. 42. Coleman DL y Ruef C: Interleukin-6: an autocrine regulator of mesangial cell growth. Kidney Int 41:604-606, 1992. 43. Zoja C, Wang JM, Bettoni S, Sironi M, Renzi D, Chiaffarino F , Abboud HE, Van Damme J, Mantovani A, Remuzzi G y Rambaldi A: Interleukin-1ß and tumor necrosis factor- induce gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells. Am J Pathol 138:991-1003, 1991. 44. Baud L, Fouqueray B, Philippe C y Amrani A: Tumor necrosis factor alpha and mesangial cells. Kidney Int 41:600-603, 1992. 45. Abboud HE, Poptic E y DiCorleto P: Production of plateletd e r i v e d growth factorlike protein by rat mesangial cells in culture. J Clin Invest 80:675-683, 1987. 46. A b b o u d HE: Growth factors in glomerulonephritis. Kidney Int 43:252-267, 1993. 47. O k u d a S, Languino LR, Ruoslahti E y Border WA: Elevated expression of transforming growth factor-ß and proteoglycan production in experimental glomerulonephritis. J Clin Invest 86:453-462, 1990. 48. A r o n DC, Rosenzweig JL y Abboud HE: Synthesis and binding of insulinlike growth factor 1 by human glomerular mesangial cells. J Clin Endocrinol Metab 68:585-591, 1989. 49. S h u l t z PJ, DiCorleto PE, Silver BJ y Abboud HE: Mesangial c e l l s express PDGF mRNAs and proliferate in response to PDGF. Am J Physiol 255:F674-F684, 1988. 12 MESANGIAL CELL PATHOPHYSIOLOGY 50. J o h n s o n RJ, Iida H, Yoshimura A, Floege J y Bowen-Pope DF: Platelet-derived growth factor (PDGF): a potentially impo rtan t cytokine in glomerular disease. Kidney Int 4 1 : 5 9 0 594, 1992. 51. Border WA, Okuda S, Languino LR, Sporn MB y Ruoslahti E: S u p p r e s s i o n of experimental glomerulonephritis by antiser u m against transforming growth factor ß1. Nature (Lond) 346:371-374, 1990. 52. Border WA, Noble NA, Yamamoto T, Harper JR, Yamaguchi Y , Pierschbacher MD y Ruoslahti E: Natural inhibitor of transforming growth factor-ß protects against scarring in exp e r i m e n t a l kidney disease. Nature (Lond) 3 6 0 : 3 6 1 - 3 6 4 , 1992. 53. Yamamoto T, Nakamura T, Noble NA, Ruoslahti E y Border WA: Expression of transforming growth factor ß is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci (USA) 90:1814-1818, 1993. 13
Idiomas
Nefrología (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.