Editing Mesangial cell

{{short description|Specialised kidney cells}}
{{Infobox cell
| Name        = Mesangial cell
| Image       = 
| Caption     = 
| Image2      =
| Caption2    =
| Precursor   =
| Location =  [[Mesangium]] of the [[glomerulus (kidney)|glomeruli]] of [[kidney]]s
}}
'''Mesangial cells'''  are specialised cells in the [[kidney]] that make up the [[mesangium]] of the [[glomerulus (kidney) |glomerulus]]. Together with the mesangial matrix, they form the [[vascular pole]] of the [[renal corpuscle]].<ref name= Banas>{{cite journal|last1=Schlondorff|first1=D|last2=Banas|first2=B|title=The Mesangial Cell Revisited: No Cell Is an Island|journal=Journal of the American Society of Nephrology|date=2009|volume=20|issue=6|pages=1179–1187|pmid=19470685|doi=10.1681/ASN.2008050549|doi-access=free}}</ref> The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus.<ref name=Scindia>{{cite journal|last1=Scindia|first1=Y|last2=Deshmukh|first2=U|last3=Bagavant|first3=H|title=Mesangial pathology in glomerular disease: targets for therapeutic intervention|journal=Advanced Drug Delivery Reviews|date=2010|volume=62|issue=14|pages=1337–1343|pmid=20828589|pmc=2992591|doi=10.1016/j.addr.2010.08.011}}</ref> Mesangial cells can be categorized as either [[extraglomerular mesangial cell]]s or [[intraglomerular mesangial cell]]s, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the [[afferent arteriole|afferent]] and [[efferent arteriole]]s towards the vascular pole of the glomerulus.<ref name=Barajas>{{cite journal|last1=Barajas|first1=L|title=Cell-specific protein and gene expression in the juxtaglomerular apparatus|journal=Clin Exp Pharmacol Physiol|date=1997|volume=24|issue=7|pages=520–526|pmid=9248671|doi= 10.1111/j.1440-1681.1997.tb01239.x|s2cid=41023701}}</ref> The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the [[capillary|capillaries]].<ref name=Goligorsky>{{cite journal|last1=Goligorsky|first1=M|last2=Iijima|first2=K|last3=Krivenko|first3=Y|last4=Tsukahara|first4=H|last5=Hu|first5=Y|last6=Moore|first6=L|title=Role of mesangial cells in macula densa to afferent arteriole information transfer|journal=Clin Exp Pharmacol Physiol|date=1997|volume=24|issue=7|pages=527–531|pmid=9248672|doi=10.1111/j.1440-1681.1997.tb01240.x|s2cid=24753189}}</ref> 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|date=May 2016}}

==Structure==
[[File:Renal corpuscle-en.svg|thumb|468x468px|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.<ref name="Takano">{{cite journal|last1=Takano|first1=K|last2=Kawasaki|first2=Y|last3=Imaizumi|first3=T|last4=Matsuura|first4=H|last5=Nozawa|first5=R|last6=Tannji|first6=M|last7=Suyama|first7=K|last8=Isome|first8=M|last9=Suzuki|first9=H|last10=Hosoya|first10=M|title=Development of Glomerular Endothelial Cells, Podocytes and Mesangial Cells in the Human Fetus and Infant|journal=The Tohoku Journal of Experimental Medicine|date=2007|volume=212|issue=1|pages=81–90|pmid=17464107|doi=10.1620/tjem.212.81|doi-access=free}}</ref> The anchoring filaments from mesangial cells to the [[glomerular basement membrane]] can alter capillary flow by changing glomerular [[ultrafiltration (renal)|ultrafiltration]] surface area.<ref name="Banas" /> Extraglomerular mesangial cells are in close connection to afferent and efferent arteriolar cells by [[gap junction]]s, allowing for intercellular communication.<ref name="Barajas" /> Mesangial cells are separated by intercellular spaces containing [[extracellular matrix]] called the mesangial matrix that is produced by the mesangial cells.<ref name="Banas" /> Mesangial matrix provides structural support for the mesangium.<ref name="Banas" /> 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 [[proteoglycan]]s.<ref name="Mason">{{cite journal|last1=Mason|first1=R|last2=Wahab|first2=N|title=Extracellular Matrix Metabolism in Diabetic Nephropathy|journal=Journal of the American Society of Nephrology|date=2003|volume=14|issue=5|pages=1358–1373|pmid=12707406|doi=10.1097/01.ASN.0000065640.77499.D7|doi-access=free}}</ref>

==Development== 
It is unclear whether the mesangial cells originate from [[mesenchyme|mesenchymal]] or [[stromal cell]]s. However there is evidence suggesting that they originate elsewhere outside of the glomerulus and then migrate into the glomerulus during development.<ref name=faa>{{cite journal|last1=Faa|first1=G|last2=Gerosa|first2=C|last3=Fanni|first3=D|last4=Monga|first4=G|last5=Zaffanello|first5=M|last6=Van Eyken|first6=P|last7=Fanos|first7=V|title=Morphogenesis and molecular mechanisms involved in human kidney development|journal=J. Cell. Physiol.|date=2011|volume=227|issue=3|pages=1257–1268|pmid=21830217|doi=10.1002/jcp.22985|s2cid=4946194}}</ref> Human foetal and infant kidneys stained for [[ACTA2 |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.<ref name=Takano/> It is possible that they share the same origin as supporting cells such as [[pericyte]]s and [[vascular smooth muscle]] cells, or even be a type of specialised vascular smooth muscle cell.<ref name=Schell>{{cite journal|last1=Schell|first1=C|last2=Wanner|first2=N|last3=Huber|first3=T|title=Glomerular development – Shaping the multi-cellular filtration unit|journal=Seminars in Cell & Developmental Biology|date=2014|volume=36|issue=2|pages=39–49|pmid=25153928|doi=10.1016/j.semcdb.2014.07.016|doi-access=free}}</ref>

==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.<ref name=Schell/> Mice lacking the growth factor PDGF-B or PDGFRβ do not develop mesangial cells.<ref name=Schell/>  When mesangial cells are absent the blood vessel becomes a single dilated vessel with up to 100-fold decrease in surface area.<ref name=Schell/> 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.<ref name=Schell/> Mesangial cell progenitors are also a target of PDGF-B and can be selected for by the signal to then develop into mesangial cells.<ref name=Lindahl>{{cite journal|last1=Lindahl|first1=P|last2=Hellstrom|first2=M|last3=Kalen|first3=M|last4=Karlsson|first4=L|last5=Pekny|first5=M|last6=Pekna|first6=M|last7=Soriano|first7=P|last8=Betsholtz|first8=C|title=Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli|journal=Development|date=1998|volume=125|issue=17|pages=3313–3322|doi=10.1242/dev.125.17.3313|pmid=9693135}}</ref>

===Interactions with other renal cells===
Mesangial cells form a glomerular functional unit with glomerular endothelial cells and [[podocyte]]s through interactions of molecular signalling pathways which are essential for the formation of the glomerular tuft.<ref name= Banas/> Mesangial cells aid filtration by constituting part of the glomerular capillary tuft structure that filters fluids to produce urine.<ref name= Vaughan>{{cite journal|last1=Vaughan|first1=M|last2=Quaggin|first2=S|title=How Do Mesangial and Endothelial Cells Form the Glomerular Tuft?|journal=Journal of the American Society of Nephrology|date=2008|volume=19|issue=1|pages=24–33|pmid=18178797|doi=10.1681/ASN.2007040471|doi-access=free}}</ref> Communication between mesangial cells and vascular smooth muscle cells via gap junctions helps regulate the process of [[tubuloglomerular feedback]] and urine formation.<ref name=Ren>{{cite journal|last1=Ren|first1=Y|last2=Carretero|first2=O|last3=Garvin|first3=J|title=Role of mesangial cells and gap junctions in tubuloglomerular feedback|journal=Kidney International|date=2002|volume=62|issue=2|pages=525–531|pmid=12110013|doi=10.1046/j.1523-1755.2002.00454.x|doi-access=free}}</ref> 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.<ref name=Ren/>

===Contractions regulate capillary flow===
Mesangial cells can contract and relax to regulate capillary flow.<ref name= Banas/> This is regulated by [[vasoactivity|vasoactive substances]].<ref name=Stockand>{{cite journal|last1=Stockand|first1=J|last2=Sansom|first2=S|title=Glomerular mesangial cells: electrophysiology and regulation of contraction|journal=Physiological Reviews|date=1998|volume=78|issue=3|pages=723–744|pmid=9674692 |doi=10.1152/physrev.1998.78.3.723}}</ref> Contraction of mesangial cells is dependent on cell membrane permeability to calcium ions and relaxation is mediated by paracrine factors, hormones and [[cyclic adenosine monophosphate|cAMP]].<ref name="Stockand"/> In response to capillary stretching, mesangial cells can respond by producing several growth factors: [[transforming growth factor|TGF]]-1, [[VEGF]] and [[CTGF|connective tissue growth factor]].<ref name= Banas/>

===Removal of macromolecules===
The mesangium is exposed to macromolecules from the capillary lumen as they are separated only by fenestrated endothelium without basement membrane.<ref name=Scindia/> 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.<ref name= Banas/> Size, charge, concentration, and affinity for mesangial cell receptors of the macromolecule affects how the macromolecule is removed.<ref name= Schlondorff>{{cite journal|last1=Schlondorff|first1=D|title=Roles of the mesangium in glomerular function|journal=Kidney International|date=1996|volume=49|issue=6|pages=1583–1585|pmid=8743459|doi=10.1038/ki.1996.229 |doi-access=free}}</ref> [[Triglyceride]]s may undergo pinocytosis and antibody [[Immunoglobulin G|IgG]] complexes may lead to activation of adhesion molecules and [[chemokine]]s by mesangial cells.<ref name= Banas/>
They also regulate glomerular filtration.

==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.<ref name=Brunskill>{{cite journal|last1=Brunskill|first1=E|last2=Potter|first2=S|title=Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy|journal=BMC Nephrol|date=2012|volume=13|issue=1|pages=70|pmid=22839765|pmc= 3416581 |doi= 10.1186/1471-2369-13-70|doi-access=free}}</ref> Mesangial expansion occurs due to increased deposition of extracellular matrix proteins, for example fibronectin, into the mesangium.<ref name=Mason/> Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by [[matrix metalloproteinase]]s.<ref name=Mason/>

Increased glucose levels results in the activation of [[metabolic pathway]]s leading to increased [[oxidative stress]].<ref name=Scindia/> This in turn results in the over-production and accumulation of advanced glycosylation end products responsible for enhancing the risk of developing glomerular diseases.<ref name=Skolnik>{{cite journal|last1=Skolnik|first1=E|last2=Yang|first2=Z|last3=Makita|first3=Z|last4=Radoff|first4=S|last5=Kirstein|first5=M|last6=Vlassara|first6=H|title=Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy|journal=Journal of Experimental Medicine|date=1991|volume=174|issue=4|pages=931–939|pmid=1655949|pmc=2118966|doi=10.1084/jem.174.4.931}}</ref> Mesangial cells grown on advanced glycosylation end product-modified matrix proteins demonstrate increased production of fibronectin and a decrease in proliferation.<ref name=Skolnik/> These factors eventually lead to the thickening of the glomerular basement membrane, mesangial matrix expansion then [[glomerulosclerosis]] and [[fibrosis]].<ref name=Kanwar>{{cite journal|last1=Kanwar|first1=Y|last2=Wada|first2=J|last3=Sun|first3=L|last4=Xie|first4=P|last5=Wallner|first5=E|last6=Chen|first6=S|last7=Chugh|first7=S|last8=Danesh|first8=F|title=Diabetic Nephropathy: Mechanisms of Renal Disease Progression|journal=Experimental Biology and Medicine|date=2008|volume=233|issue=1|pages=4–11|pmid=18156300|doi=10.3181/0705-MR-134|s2cid=15349392}}</ref>

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.<ref name=Kanwar/> 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.<ref name=Kanwar/>

== See also ==
*[[List of human cell types derived from the germ layers]]
*[[List of distinct cell types in the adult human body]]

== References ==
{{reflist}}


[[Category:Cell biology]]
[[Category:Human cells]]