Mesangial cells are specialised cells in the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

that make up the

mesangium The glomerulus (plural glomeruli) 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 s ...

of the

glomerulus ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filt ...

. Together with the mesangial matrix, they form the vascular pole of the

renal corpuscle A renal corpuscle (also called malpighian body) 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 capsul ...

. The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus. Mesangial cells can be categorized as either

extraglomerular mesangial cell Extraglomerular mesangial cells (also known as Lacis cells, Polkissen cells, or Goormaghtigh cells) are light-staining pericytes in the kidney found outside the glomerulus, near the vascular pole. They resemble smooth muscle cells and play a rol ...

s or

intraglomerular mesangial cell Intraglomerular mesangial cells are located among the glomerular capillaries within a renal corpuscle of a kidney. Characteristics Mesangial cells are macrophages and resemble pericytes. They typically cover 30% of glomerular capillaries. T ...

s, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and

efferent arteriole The efferent arterioles are blood vessels that are part of the urinary tract of organisms. Efferent (from Latin ex + ferre) means "outgoing", in this case meaning carrying blood out away from the glomerulus. The efferent arterioles form a conve ...

s towards the vascular pole of the glomerulus. The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries. 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.

Structure

Mesangial cells have irregular shapes with flattened-cylinder-like cell bodies and processes at both ends containing

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

myosin Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin (M ...

and

actinin Actinin is a microfilament protein. Alpha-actinin-1 is necessary for the attachment of actin myofilaments to the Z-lines in skeletal muscle cells, and to the dense bodies in smooth muscle cells. The functional protein is an anti-parallel dimer ...

, giving mesangial cells contractile properties. The anchoring filaments from mesangial cells to the

glomerular basement membrane 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 g ...

can alter capillary flow by changing glomerular

ultrafiltration Ultrafiltration (UF) is a variety of membrane filtration in which forces such as pressure or concentration gradients lead to a separation through a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained in the ...

surface area. Extraglomerular mesangial cells are in close connection to afferent and efferent arteriolar cells by

gap junction Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regula ...

s, allowing for intercellular communication. Mesangial cells are separated by intercellular spaces containing

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struct ...

called the mesangial matrix that is produced by the mesangial cells. Mesangial matrix provides structural support for the mesangium. Mesangial matrix is composed of glomerular matrix proteins such as collagen IV (α1 and α2 chains), collagen V, collagen VI,

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...

A, B1, B2,

fibronectin Fibronectin is a high-molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collagen ...

, and

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whi ...

Development

It is unclear whether the mesangial cells originate from

mesenchymal Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...

stromal cell Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine muco ...

s. However there is evidence suggesting that they originate elsewhere outside of the glomerulus and then migrate into the glomerulus during development. 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. It is possible that they share the same origin as supporting cells such as

pericyte Pericytes (previously known as Rouget cells) 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 ...

s and

vascular smooth muscle Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood ...

cells, or even be a type of specialised vascular smooth muscle cell.

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 Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing bloo ...

(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. Mice lacking the growth factor PDGF-B or PDGFRβ do not develop mesangial cells. When mesangial cells are absent the blood vessel becomes a single dilated vessel with up to 100-fold decrease in surface area. 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. Mesangial cell progenitors are also a target of PDGF-B and can be selected for by the signal to then develop into mesangial cells.

Interactions with other renal cells

Mesangial cells form a glomerular functional unit with glomerular endothelial cells and

podocyte 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 fi ...

s through interactions of molecular signalling pathways which are essential for the formation of the glomerular tuft. Mesangial cells aid filtration by constituting part of the glomerular capillary tuft structure that filters fluids to produce urine. Communication between mesangial cells and vascular smooth muscle cells via gap junctions helps regulate the process of

tubuloglomerular feedback In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules (a downstream area of the tubular fluid) is signaled to the glomerulus (an upstream a ...

and urine formation. Damage to mesangial cells using Thy 1-1 antibody specific to mesangial cells causes the

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

of arterioles mediated by tubuloglomerular feedback to be lost.

Contractions regulate capillary flow

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

VEGF Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...

and

connective tissue growth factor CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein). CTGF has important roles in many ...

Removal of macromolecules

The mesangium is exposed to macromolecules from the capillary lumen as they are separated only by fenestrated endothelium without basement membrane. Mesangial cells play a role in restricting macromolecules from accumulating in the mesangial space by receptor- independent uptake processes of

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is c ...

, micro- and macro-

pinocytosis In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell ...

, or receptor-dependent processes and then transported along the mesangial stalk. Size, charge, concentration, and affinity for mesangial cell receptors of the macromolecule affects how the macromolecule is removed.

Triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...

s may undergo pinocytosis and antibody

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...

complexes may lead to activation of adhesion molecules and

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

s by mesangial cells.

Clinical significance

Diabetic nephropathy

The expansion of mesangial matrix is one characteristic of

diabetic nephropathy 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 ...

although it also involves other cells in interaction including podocytes and endothelial cells. Mesangial expansion occurs due to increased deposition of extracellular matrix proteins, for example fibronectin, into the mesangium. Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by

matrix metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs ...

s. Increased glucose levels results in the activation of

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical rea ...

s leading to increased

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...

. This in turn results in the over-production and accumulation of advanced glycosylation end products responsible for enhancing the risk of developing glomerular diseases. Mesangial cells grown on advanced glycosylation end product-modified matrix proteins demonstrate increased production of fibronectin and a decrease in proliferation. These factors eventually lead to the thickening of the glomerular basement membrane, mesangial matrix expansion then

glomerulosclerosis Glomerulosclerosis is the hardening of the glomeruli in the kidney. It is a general term to describe scarring of the kidneys' tiny blood vessels, the glomeruli, the functional units in the kidney that filter urea from the blood. Proteinuria (l ...

and

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

. Mesangial pathologies may also develop during the early phase of diabetes. Glomerular hypertension causes mesangial cells to stretch which causes induced expression of

GLUT1 Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose acros ...

leading to increased cellular glucose. 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.

References

{{reflist Cell biology