Myofibroblast
Encyclopedia
A Myofibroblast is a cell that is in between a fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

 and a smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

 cell in differentiation.

Developmental origin

There are many possible ways of myofibroblast development:
  1. Partial smooth muscle differentiation of a fibroblastic cell
  2. Activation of a stellate cell (eg Hepatic Ito cells
    Hepatic stellate cell
    Hepatic stellate cells , also known as perisinusoidal cells or Ito cells , are pericytes found in the perisinusoidal space of the liver also known as the space of Disse...

     or pancreatic stellate cells).
  3. Loss of contractile phenotype (or acquisition of "synthetic phenotype") of a smooth muscle cell.
  4. Direct myofibroblastic differentiation of a progenitor cell resident in a stromal tissue.
  5. Homing and recruitment of a circulating mesenchymal precursor which can directly differentiate as above or indirectly differentiate through the other cell types as intermediates.
  6. Epithelial to mesenchymal transdifferentiation of an epithelial cell.

Markers

Myofibroblasts usually stain for the intermediate filament vimentin
Vimentin
Vimentin is a type III intermediate filament protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton...

 which is a general mesenchymal marker and "alpha smooth muscle actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

". They are positive for other smooth markers like another intermediate filament type desmin
Desmin
Desmin is a protein that in humans is encoded by the DES gene.Desmin is a type III intermediate filament found near the Z line in sarcomeres. It was first described in 1976, first purified in 1977, the gene was cloned in 1989, and the first knock-out mouse was created in 1996. Desmin is only...

 positive in some tissues but may be negative for desmin in some others. Similar heterogeneous positivity may exist for almost every smooth muscle marker except probably a few which are positive only in contractile smooth muscles like metavinculin and smoothelin. Some myofibroblasts (esp if they have a stellate form) may also be positive for GFAP.

Location and function

Myofibroblasts are found subepithelially in many mucosal surfaces - for example, throughout almost the whole of the gastrointestinal and genitourinary tracts. Here they not only act as a regulator of the shape of the crypts and villi but also act as stem-niche cells in the intestinal crypts and as parts of atypical antigen presenting cells. They have both support as well as paracrine function in most places. In many organs like liver, lung, and kidney they are primarily involved in fibrosis. In the wound tissue they are implicated in wound strengthening by extracellular collagen fiber deposition and then wound contraction by intracellular contraction and concomitant alignment of the collagen fibers by integrin mediated pulling on to the collagen bundles. Pericytes and renal mesangial cells are some examples of modified myofibroblast like cells.

Myofibroblasts may interfere with the propagation of electrical signals controlling heart rhythm, leading to arrhythmia in both patients who have suffered a heart attack and in foetuses. Ursodiol
Ursodiol
Ursodiol, also known as ursodeoxycholic acid and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria.-Endogenous effects:...

 is a promising drug for this condition.

Myofibroblasts in wound healing

It can contract by using smooth muscle type actin-myosin complex, rich in a form of actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

 called alpha-smooth muscle actin. These cells are then capable of speeding wound repair by contracting the edges of the wound.

Early work on wound healing showed that granulation tissue
Granulation tissue
Granulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size it heals...

 taken from a wound, could contract in vitro (or in an organ bath) in a similar fashion to smooth muscle, when exposed to substances that cause smooth muscle to contract, such as adrenaline or angiotensin
Angiotensin
Angiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...

.

More recently it has been shown that fibroblasts can transform into myofibroblasts with photobiomodulation.

After healing is complete, these cells are lost through apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 and it has been suggested that in several fibrotic diseases (for example liver cirrhosis, kidney fibrosis, retroperitoneal fibrosis) that this mechanism fails to work, leading to persistence of the myofibroblasts, and consequently expansion of the extracellular matrix (fibrosis) and contraction.

Similarly, in wounds that fail to resolve and become keloids or hypertrophic scars, myofibroblasts may persist, rather than disappearing by apoptosis.
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