Mesangial cell

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Mesangial cell
Details
Location Mesangium of the glomeruli of kidneys
Identifiers
MeSH D050527
FMA 70972
Anatomical terms of microanatomy

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 ]

Contents

Structure

Mesangial cells (colored in purple) as seen within intraglomerular and extraglomerular mesangium. Renal corpuscle-en.svg
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] 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. [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

Related Research Articles

<span class="mw-page-title-main">Capillary</span> Smallest type of blood vessel

A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: they convey blood between the arterioles and venules. These microvessels are the site of exchange of many substances with the interstitial fluid surrounding them. Substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in the microcirculation.

<span class="mw-page-title-main">Nephron</span> Microscopic structural and functional unit of the kidney.

The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged ; first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.

<span class="mw-page-title-main">Juxtaglomerular apparatus</span> Structure that regulates function of each nephron

The juxtaglomerular apparatus is a structure in the kidney that regulates the function of each nephron, the functional units of the kidney. The juxtaglomerular apparatus is named because it is next to (juxta-) the glomerulus.

<span class="mw-page-title-main">Bowman's capsule</span>

Bowman's capsule is a cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of blood to form urine. A glomerulus is enclosed in the sac. Fluids from blood in the glomerulus are collected in the Bowman's capsule.

<span class="mw-page-title-main">Renal corpuscle</span> Blood-filtering component of the nephron of the kidney

A renal corpuscle is the blood-filtering component of the nephron of the kidney. It consists of a glomerulus - a tuft of capillaries composed of endothelial cells, and a glomerular capsule known as Bowman's capsule.

<span class="mw-page-title-main">Glomerulus (kidney)</span> Functional unit of nephron

The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.

<span class="mw-page-title-main">IgA nephropathy</span> Disease of the kidney

IgA nephropathy (IgAN), also known as Berger's disease, or synpharyngitic glomerulonephritis, is a disease of the kidney and the immune system; specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney. Aggressive Berger's disease can attack other major organs, such as the liver, skin and heart.

<span class="mw-page-title-main">Podocyte</span> Type of kidney cell

Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large molecules such as proteins while smaller molecules such as water, salts, and sugars are filtered as the first step in the formation of urine. Although various viscera have epithelial layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is podocalyxin.

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">Diabetic nephropathy</span> Chronic loss of kidney function

Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine, rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.

<span class="mw-page-title-main">Hypertensive kidney disease</span> Medical condition

Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis. It should be distinguished from renovascular hypertension, which is a form of secondary hypertension, and thus has opposite direction of causation.

<span class="mw-page-title-main">Membranous glomerulonephritis</span> Medical condition

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people.

<span class="mw-page-title-main">Pericyte</span> Cells associated with capillary linings

Pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood capillaries, where they communicate with endothelial cells by means of both direct physical contact and paracrine signaling. The morphology, distribution, density and molecular fingerprints of pericytes vary between organs and vascular beds. Pericytes help to maintain homeostatic and hemostatic functions in the brain, one of the organs with higher pericyte coverage, and also sustain the blood–brain barrier. These cells are also a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. Pericytes have been postulated to regulate capillary blood flow and the clearance and phagocytosis of cellular debris in vitro. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signaling. A deficiency of pericytes in the central nervous system can cause increased permeability of the blood–brain barrier.

In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules is signaled to the glomerulus. Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level.

<span class="mw-page-title-main">Intraglomerular mesangial cell</span>

Intraglomerular mesangial cells are located among the glomerular capillaries within a renal corpuscle of a kidney.

<span class="mw-page-title-main">Glomerular basement membrane</span>

The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomerular basement membrane, and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that forms in Bowman's capsule. The glomerular basement membrane is a fusion of the endothelial cell and podocyte basal laminas, and is the main site of restriction of water flow. Glomerular basement membrane is secreted and maintained by podocyte cells.

<span class="mw-page-title-main">Ultrafiltration (kidney)</span>

In renal physiology, ultrafiltration occurs at the barrier between the blood and the filtrate in the glomerular capsule in the kidneys. As in nonbiological examples of ultrafiltration, pressure and concentration gradients lead to a separation through a semipermeable membrane. The Bowman's capsule contains a dense capillary network called the glomerulus. Blood flows into these capillaries through the afferent arterioles and leaves through the efferent arterioles.

Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Symptoms may develop in the first few months of life or later in childhood.

<span class="mw-page-title-main">Mesangial proliferative glomerulonephritis</span> Medical condition

Mesangial proliferative glomerulonephritis (MesPGN) is a morphological pattern characterized by a numerical increase in mesangial cells and expansion of the extracellular matrix within the mesangium of the glomerulus. The increase in the number of mesangial cells can be diffuse or local and immunoglobulin and/or complement deposition can also occur. MesPGN is associated with a variety of disease processes affecting the glomerulus, though can be idiopathic. The clinical presentation of MesPGN usually consists of hematuria or nephrotic syndrome. Treatment is often consistent with the histologic pattern of and/or disease process contributing to mesangial proliferative glomerulonephritis, and usually involves some form of immunosuppressant.

Catharine Isobel Whiteside, CM, FRCPC, FCAHS is a Canadian physician and medical researcher. She is Director, Strategic Partnerships of Diabetes Action Canada and Chair of the board of the Banting Research Foundation. Whiteside is the former Dean of the Faculty of Medicine at the University of Toronto.

References

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  2. 1 2 3 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.
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  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. S2CID   24753189.
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  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. S2CID   4946194.
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  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. doi:10.1242/dev.125.17.3313. 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. 1 2 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. 1 2 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. 1 2 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. 1 2 3 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. S2CID   15349392.
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