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Mesangial cell

February 01, 2023

Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle.[1] The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus.[2] Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus.[3] The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries.[4] The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris. The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus.[citation needed]

Mesangial cell
Details
LocationMesangium of the glomeruli of kidneys
Identifiers
MeSHD050527
FMA70972
Anatomical terms of microanatomy
[edit on Wikidata]

Structure

 
Mesangial cells (colored in purple) as seen within intraglomerular and extraglomerular mesangium.

Mesangial cells have irregular shapes with flattened-cylinder-like cell bodies and processes at both ends containing actin, myosin and actinin, giving mesangial cells contractile properties.[5] The anchoring filaments from mesangial cells to the glomerular basement membrane can alter capillary flow by changing glomerular ultrafiltration surface area.[1] Extraglomerular mesangial cells are in close connection to afferent and efferent arteriolar cells by gap junctions, allowing for intercellular communication.[3] Mesangial cells are separated by intercellular spaces containing extracellular matrix called the mesangial matrix that is produced by the mesangial cells.[1] Mesangial matrix provides structural support for the mesangium.[1] Mesangial matrix is composed of glomerular matrix proteins such as collagen IV (α1 and α2 chains), collagen V, collagen VI, laminin A, B1, B2, fibronectin, and proteoglycans.[6]

Development

It is unclear whether the mesangial cells originate from mesenchymal or stromal cells. However there is evidence suggesting that they originate elsewhere outside of the glomerulus and then migrate into the glomerulus during development.[7] Human foetal and infant kidneys stained for alpha smooth muscle actin (α-SMA), a marker for mesangial cells, demonstrated that α-SMA-positive mesenchymal cells migrate towards the glomerulus and during a later stage they can be found within the mesangium.[5] It is possible that they share the same origin as supporting cells such as pericytes and vascular smooth muscle cells, or even be a type of specialised vascular smooth muscle cell.[8]

Function

Formation of capillary loops during development

During development mesangial cells are important in the formation of convoluted capillaries allowing for efficient diffusion to occur. Endothelial precursor cells secrete platelet-derived growth factor (PDGF)-B and mesangial cells have receptors for PDGF. This induces mesangial cells to attach to endothelial cells causing developing blood vessels to loop resulting in convoluted capillaries.[8] Mice lacking the growth factor PDGF-B or PDGFRβ do not develop mesangial cells.[8] When mesangial cells are absent the blood vessel becomes a single dilated vessel with up to 100-fold decrease in surface area.[8] The transcription factor for PDGFRβ, Tbx18, is crucial for the development of mesangial cells. Without Tbx18 the development of mesangial cells is compromised and results in the formation of dilated loops.[8] Mesangial cell progenitors are also a target of PDGF-B and can be selected for by the signal to then develop into mesangial cells.[9]

Interactions with other renal cells

Mesangial cells form a glomerular functional unit with glomerular endothelial cells and podocytes through interactions of molecular signalling pathways which are essential for the formation of the glomerular tuft.[1] Mesangial cells aid filtration by constituting part of the glomerular capillary tuft structure that filters fluids to produce urine.[10] Communication between mesangial cells and vascular smooth muscle cells via gap junctions helps regulate the process of tubuloglomerular feedback and urine formation.[11] Damage to mesangial cells using Thy 1-1 antibody specific to mesangial cells causes the vasoconstriction of arterioles mediated by tubuloglomerular feedback to be lost.[11]

Contractions regulate capillary flow

Mesangial cells can contract and relax to regulate capillary flow.[1] This is regulated by vasoactive substances.[12] Contraction of mesangial cells is dependent on cell membrane permeability to calcium ions and relaxation is mediated by paracrine factors, hormones and cAMP.[12] In response to capillary stretching, mesangial cells can respond by producing several growth factors: TGF-1, VEGF and connective tissue growth factor.[1]

Removal of macromolecules

The mesangium is exposed to macromolecules from the capillary lumen as they are separated only by fenestrated endothelium without basement membrane.[2] Mesangial cells play a role in restricting macromolecules from accumulating in the mesangial space by receptor- independent uptake processes of phagocytosis, micro- and macro-pinocytosis, or receptor-dependent processes and then transported along the mesangial stalk.[1] Size, charge, concentration, and affinity for mesangial cell receptors of the macromolecule affects how the macromolecule is removed.[13] Triglycerides may undergo pinocytosis and antibody IgG complexes may lead to activation of adhesion molecules and chemokines by mesangial cells.[1]

Clinical significance

Diabetic nephropathy

The expansion of mesangial matrix is one characteristic of diabetic nephropathy although it also involves other cells in interaction including podocytes and endothelial cells.[14] Mesangial expansion occurs due to increased deposition of extracellular matrix proteins, for example fibronectin, into the mesangium.[6] Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by matrix metalloproteinases.[6]

Increased glucose levels results in the activation of metabolic pathways leading to increased oxidative stress.[2] This in turn results in the over-production and accumulation of advanced glycosylation end products responsible for enhancing the risk of developing glomerular diseases.[15] Mesangial cells grown on advanced glycosylation end product-modified matrix proteins demonstrate increased production of fibronectin and a decrease in proliferation.[15] These factors eventually lead to the thickening of the glomerular basement membrane, mesangial matrix expansion then glomerulosclerosis and fibrosis.[16]

Mesangial pathologies may also develop during the early phase of diabetes. Glomerular hypertension causes mesangial cells to stretch which causes induced expression of GLUT1 leading to increased cellular glucose.[16] The repetition of stretching and relaxation cycle of mesangial cells due to hypertension increases mesangial cell proliferation and the production of extracellular matrix which can then accumulate and lead to glomerular disease.[16]

See also

References

  1. ^ a b c d e f g h i Schlondorff, D; Banas, B (2009). "The Mesangial Cell Revisited: No Cell Is an Island". Journal of the American Society of Nephrology. 20 (6): 1179–1187. doi:10.1681/ASN.2008050549. PMID 19470685.
  2. ^ a b c Scindia, Y; Deshmukh, U; Bagavant, H (2010). "Mesangial pathology in glomerular disease: targets for therapeutic intervention". Advanced Drug Delivery Reviews. 62 (14): 1337–1343. doi:10.1016/j.addr.2010.08.011. PMC 2992591. PMID 20828589.
  3. ^ a b Barajas, L (1997). "Cell-specific protein and gene expression in the juxtaglomerular apparatus". Clin Exp Pharmacol Physiol. 24 (7): 520–526. doi:10.1111/j.1440-1681.1997.tb01239.x. PMID 9248671.
  4. ^ Goligorsky, M; Iijima, K; Krivenko, Y; Tsukahara, H; Hu, Y; Moore, L (1997). "Role of mesangial cells in macula densa to afferent arteriole information transfer". Clin Exp Pharmacol Physiol. 24 (7): 527–531. doi:10.1111/j.1440-1681.1997.tb01240.x. PMID 9248672.
  5. ^ a b Takano, K; Kawasaki, Y; Imaizumi, T; Matsuura, H; Nozawa, R; Tannji, M; Suyama, K; Isome, M; Suzuki, H; Hosoya, M (2007). "Development of Glomerular Endothelial Cells, Podocytes and Mesangial Cells in the Human Fetus and Infant". The Tohoku Journal of Experimental Medicine. 212 (1): 81–90. doi:10.1620/tjem.212.81. PMID 17464107.
  6. ^ a b c Mason, R; Wahab, N (2003). "Extracellular Matrix Metabolism in Diabetic Nephropathy". Journal of the American Society of Nephrology. 14 (5): 1358–1373. doi:10.1097/01.ASN.0000065640.77499.D7. PMID 12707406.
  7. ^ Faa, G; Gerosa, C; Fanni, D; Monga, G; Zaffanello, M; Van Eyken, P; Fanos, V (2011). "Morphogenesis and molecular mechanisms involved in human kidney development". J. Cell. Physiol. 227 (3): 1257–1268. doi:10.1002/jcp.22985. PMID 21830217.
  8. ^ a b c d e Schell, C; Wanner, N; Huber, T (2014). "Glomerular development – Shaping the multi-cellular filtration unit". Seminars in Cell & Developmental Biology. 36 (2): 39–49. doi:10.1016/j.semcdb.2014.07.016. PMID 25153928.
  9. ^ Lindahl, P; Hellstrom, M; Kalen, M; Karlsson, L; Pekny, M; Pekna, M; Soriano, P; Betsholtz, C (1998). "Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli". Development. 125 (17): 3313–3322. PMID 9693135.
  10. ^ Vaughan, M; Quaggin, S (2008). "How Do Mesangial and Endothelial Cells Form the Glomerular Tuft?". Journal of the American Society of Nephrology. 19 (1): 24–33. doi:10.1681/ASN.2007040471. PMID 18178797.
  11. ^ a b Ren, Y; Carretero, O; Garvin, J (2002). "Role of mesangial cells and gap junctions in tubuloglomerular feedback". Kidney International. 62 (2): 525–531. doi:10.1046/j.1523-1755.2002.00454.x. PMID 12110013.
  12. ^ a b Stockand, J; Sansom, S (1998). "Glomerular mesangial cells: electrophysiology and regulation of contraction". Physiological Reviews. 78 (3): 723–744. doi:10.1152/physrev.1998.78.3.723. PMID 9674692.
  13. ^ Schlondorff, D (1996). "Roles of the mesangium in glomerular function". Kidney International. 49 (6): 1583–1585. doi:10.1038/ki.1996.229. PMID 8743459.
  14. ^ Brunskill, E; Potter, S (2012). "Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy". BMC Nephrol. 13 (1): 70. doi:10.1186/1471-2369-13-70. PMC 3416581. PMID 22839765.
  15. ^ a b Skolnik, E; Yang, Z; Makita, Z; Radoff, S; Kirstein, M; Vlassara, H (1991). "Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy". Journal of Experimental Medicine. 174 (4): 931–939. doi:10.1084/jem.174.4.931. PMC 2118966. PMID 1655949.
  16. ^ a b c Kanwar, Y; Wada, J; Sun, L; Xie, P; Wallner, E; Chen, S; Chugh, S; Danesh, F (2008). "Diabetic Nephropathy: Mechanisms of Renal Disease Progression". Experimental Biology and Medicine. 233 (1): 4–11. doi:10.3181/0705-MR-134. PMID 18156300.

February 01, 2023
mesangial, cell, specialised, cells, kidney, that, make, mesangium, glomerulus, together, with, mesangial, matrix, they, form, vascular, pole, renal, corpuscle, mesangial, cell, population, accounts, approximately, total, cells, glomerulus, categorized, either. Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus Together with the mesangial matrix they form the vascular pole of the renal corpuscle 1 The mesangial cell population accounts for approximately 30 40 of the total cells in the glomerulus 2 Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells based on their relative location to the glomerulus The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus 3 The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries 4 The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus citation needed Mesangial cellDetailsLocationMesangium of the glomeruli of kidneysIdentifiersMeSHD050527FMA70972Anatomical terms of microanatomy edit on Wikidata Contents 1 Structure 2 Development 3 Function 3 1 Formation of capillary loops during development 3 2 Interactions with other renal cells 3 3 Contractions regulate capillary flow 3 4 Removal of macromolecules 4 Clinical significance 4 1 Diabetic nephropathy 5 See also 6 ReferencesStructure Edit Mesangial cells colored in purple as seen within intraglomerular and extraglomerular mesangium Mesangial cells have irregular shapes with flattened cylinder like cell bodies and processes at both ends containing actin myosin and actinin giving mesangial cells contractile properties 5 The anchoring filaments from mesangial cells to the glomerular basement membrane can alter capillary flow by changing glomerular ultrafiltration surface area 1 Extraglomerular mesangial cells are in close connection to afferent and efferent arteriolar cells by gap junctions allowing for intercellular communication 3 Mesangial cells are separated by intercellular spaces containing extracellular matrix called the mesangial matrix that is produced by the mesangial cells 1 Mesangial matrix provides structural support for the mesangium 1 Mesangial matrix is composed of glomerular matrix proteins such as collagen IV a1 and a2 chains collagen V collagen VI laminin A B1 B2 fibronectin and proteoglycans 6 Development EditIt is unclear whether the mesangial cells originate from mesenchymal or stromal cells However there is evidence suggesting that they originate elsewhere outside of the glomerulus and then migrate into the glomerulus during development 7 Human foetal and infant kidneys stained for alpha smooth muscle actin a SMA a marker for mesangial cells demonstrated that a SMA positive mesenchymal cells migrate towards the glomerulus and during a later stage they can be found within the mesangium 5 It is possible that they share the same origin as supporting cells such as pericytes and vascular smooth muscle cells or even be a type of specialised vascular smooth muscle cell 8 Function EditFormation of capillary loops during development Edit During development mesangial cells are important in the formation of convoluted capillaries allowing for efficient diffusion to occur Endothelial precursor cells secrete platelet derived growth factor PDGF B and mesangial cells have receptors for PDGF This induces mesangial cells to attach to endothelial cells causing developing blood vessels to loop resulting in convoluted capillaries 8 Mice lacking the growth factor PDGF B or PDGFRb do not develop mesangial cells 8 When mesangial cells are absent the blood vessel becomes a single dilated vessel with up to 100 fold decrease in surface area 8 The transcription factor for PDGFRb Tbx18 is crucial for the development of mesangial cells Without Tbx18 the development of mesangial cells is compromised and results in the formation of dilated loops 8 Mesangial cell progenitors are also a target of PDGF B and can be selected for by the signal to then develop into mesangial cells 9 Interactions with other renal cells Edit Mesangial cells form a glomerular functional unit with glomerular endothelial cells and podocytes through interactions of molecular signalling pathways which are essential for the formation of the glomerular tuft 1 Mesangial cells aid filtration by constituting part of the glomerular capillary tuft structure that filters fluids to produce urine 10 Communication between mesangial cells and vascular smooth muscle cells via gap junctions helps regulate the process of tubuloglomerular feedback and urine formation 11 Damage to mesangial cells using Thy 1 1 antibody specific to mesangial cells causes the vasoconstriction of arterioles mediated by tubuloglomerular feedback to be lost 11 Contractions regulate capillary flow Edit Mesangial cells can contract and relax to regulate capillary flow 1 This is regulated by vasoactive substances 12 Contraction of mesangial cells is dependent on cell membrane permeability to calcium ions and relaxation is mediated by paracrine factors hormones and cAMP 12 In response to capillary stretching mesangial cells can respond by producing several growth factors TGF 1 VEGF and connective tissue growth factor 1 Removal of macromolecules Edit The mesangium is exposed to macromolecules from the capillary lumen as they are separated only by fenestrated endothelium without basement membrane 2 Mesangial cells play a role in restricting macromolecules from accumulating in the mesangial space by receptor independent uptake processes of phagocytosis micro and macro pinocytosis or receptor dependent processes and then transported along the mesangial stalk 1 Size charge concentration and affinity for mesangial cell receptors of the macromolecule affects how the macromolecule is removed 13 Triglycerides may undergo pinocytosis and antibody IgG complexes may lead to activation of adhesion molecules and chemokines by mesangial cells 1 Clinical significance EditDiabetic nephropathy Edit The expansion of mesangial matrix is one characteristic of diabetic nephropathy although it also involves other cells in interaction including podocytes and endothelial cells 14 Mesangial expansion occurs due to increased deposition of extracellular matrix proteins for example fibronectin into the mesangium 6 Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by matrix metalloproteinases 6 Increased glucose levels results in the activation of metabolic pathways leading to increased oxidative stress 2 This in turn results in the over production and accumulation of advanced glycosylation end products responsible for enhancing the risk of developing glomerular diseases 15 Mesangial cells grown on advanced glycosylation end product modified matrix proteins demonstrate increased production of fibronectin and a decrease in proliferation 15 These factors eventually lead to the thickening of the glomerular basement membrane mesangial matrix expansion then glomerulosclerosis and fibrosis 16 Mesangial pathologies may also develop during the early phase of diabetes Glomerular hypertension causes mesangial cells to stretch which causes induced expression of GLUT1 leading to increased cellular glucose 16 The repetition of stretching and relaxation cycle of mesangial cells due to hypertension increases mesangial cell proliferation and the production of extracellular matrix which can then accumulate and lead to glomerular disease 16 See also EditList of human cell types derived from the germ layersReferences Edit a b c d e f g h i Schlondorff D Banas B 2009 The Mesangial Cell Revisited No Cell Is an Island Journal of the American Society of Nephrology 20 6 1179 1187 doi 10 1681 ASN 2008050549 PMID 19470685 a b c Scindia Y Deshmukh U Bagavant H 2010 Mesangial pathology in glomerular disease targets for therapeutic intervention Advanced Drug Delivery Reviews 62 14 1337 1343 doi 10 1016 j addr 2010 08 011 PMC 2992591 PMID 20828589 a b Barajas L 1997 Cell specific protein and gene expression in the juxtaglomerular apparatus Clin Exp Pharmacol Physiol 24 7 520 526 doi 10 1111 j 1440 1681 1997 tb01239 x PMID 9248671 Goligorsky M Iijima K Krivenko Y Tsukahara H Hu Y Moore L 1997 Role of mesangial cells in macula densa to afferent arteriole information transfer Clin Exp Pharmacol Physiol 24 7 527 531 doi 10 1111 j 1440 1681 1997 tb01240 x PMID 9248672 a b Takano K Kawasaki Y Imaizumi T Matsuura H Nozawa R Tannji M Suyama K Isome M Suzuki H Hosoya M 2007 Development of Glomerular Endothelial Cells Podocytes and Mesangial Cells in the Human Fetus and Infant The Tohoku Journal of Experimental Medicine 212 1 81 90 doi 10 1620 tjem 212 81 PMID 17464107 a b c Mason R Wahab N 2003 Extracellular Matrix Metabolism in Diabetic Nephropathy Journal of the American Society of Nephrology 14 5 1358 1373 doi 10 1097 01 ASN 0000065640 77499 D7 PMID 12707406 Faa G Gerosa C Fanni D Monga G Zaffanello M Van Eyken P Fanos V 2011 Morphogenesis and molecular mechanisms involved in human kidney development J Cell Physiol 227 3 1257 1268 doi 10 1002 jcp 22985 PMID 21830217 a b c d e Schell C Wanner N Huber T 2014 Glomerular development Shaping the multi cellular filtration unit Seminars in Cell amp Developmental Biology 36 2 39 49 doi 10 1016 j semcdb 2014 07 016 PMID 25153928 Lindahl P Hellstrom M Kalen M Karlsson L Pekny M Pekna M Soriano P Betsholtz C 1998 Paracrine PDGF B PDGF Rbeta signaling controls mesangial cell development in kidney glomeruli Development 125 17 3313 3322 PMID 9693135 Vaughan M Quaggin S 2008 How Do Mesangial and Endothelial Cells Form the Glomerular Tuft Journal of the American Society of Nephrology 19 1 24 33 doi 10 1681 ASN 2007040471 PMID 18178797 a b Ren Y Carretero O Garvin J 2002 Role of mesangial cells and gap junctions in tubuloglomerular feedback Kidney International 62 2 525 531 doi 10 1046 j 1523 1755 2002 00454 x PMID 12110013 a b Stockand J Sansom S 1998 Glomerular mesangial cells electrophysiology and regulation of contraction Physiological Reviews 78 3 723 744 doi 10 1152 physrev 1998 78 3 723 PMID 9674692 Schlondorff D 1996 Roles of the mesangium in glomerular function Kidney International 49 6 1583 1585 doi 10 1038 ki 1996 229 PMID 8743459 Brunskill E Potter S 2012 Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy BMC Nephrol 13 1 70 doi 10 1186 1471 2369 13 70 PMC 3416581 PMID 22839765 a b Skolnik E Yang Z Makita Z Radoff S Kirstein M Vlassara H 1991 Human and rat mesangial cell receptors for glucose modified proteins potential role in kidney tissue remodelling and diabetic nephropathy Journal of Experimental Medicine 174 4 931 939 doi 10 1084 jem 174 4 931 PMC 2118966 PMID 1655949 a b c Kanwar Y Wada J Sun L Xie P Wallner E Chen S Chugh S Danesh F 2008 Diabetic Nephropathy Mechanisms of Renal Disease Progression Experimental Biology and Medicine 233 1 4 11 doi 10 3181 0705 MR 134 PMID 18156300 Retrieved from https en wikipedia org w index php title Mesangial cell amp oldid 1122205223, wikipedia, wiki, book, books, library,

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