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| Myofibroblast | |
|---|---|
 Histological section through testicular parenchyma of aboar. 1 Lumen oftubulus seminiferus contortus, 2spermatids, 3spermatocytes, 4spermatogonia, 5Sertoli cell, 6Myofibroblasts, 7Leydig cells, 8capillaries | |
| Details | |
| Identifiers | |
| Latin | myofibroblastus |
| MeSH | D058628 |
| TH | H2.00.03.0.01013 |
| Anatomical terms of microanatomy | |
Amyofibroblast is a cellphenotype that was first described as being in a state between afibroblast and asmooth muscle cell.
Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-smooth muscle actin within their cytoplasmicstress fibers.[1]
In the gastrointestinal and genitourinary tracts, myofibroblasts are found subepithelially in mucosal surfaces. Here they not only act as a regulator of the shape of the crypts and villi, but also act as stem-niche cells in theintestinal crypts and as parts of atypical antigen-presenting cells. They have both support as well as paracrine function in most places.
Myofibroblasts were first identified in granulation tissue during skin wound healing.[2] Typically, these cells are found in granulation tissue, scar tissue (fibrosis) and the stroma of tumours. They also line the gastrointestinal tract, wherein they regulate the shapes of crypts and villi.
Myofibroblasts usually stain for the intermediate filamentvimentin, which is a general mesenchymal marker,α-smooth muscle actin (human gene =ACTA2), and forpalladin, which is a cytoskeletal actinscaffold protein. They are positive for other smooth muscle markers, such as intermediate filament typedesmin in some tissues, but may be negative for desmin in other tissues. Similar heterogeneous positivity may exist for almost every smooth muscle marker except probably a few which are positive only in contractile smooth muscles likemetavinculin andsmoothelin.
Myofibroblasts upregulate the expression offibronectin,collagens, andhyaluronic acid during and after their differentiation from fibroblasts. Among these, the EDA isoform of fibronectin (EDA-FN), and collagen type I (COL1A1/COL1A2) are typical markers of myofibroblast-dependent synthesis of pro-fibrotic extracellular matrix.
Some myofibroblasts (especially if they have a stellate form) may also be positive forGFAP.
There are many possible ways of myofibroblast development:
Perhaps the most studied pathway of myofibroblast formation isTGF-beta1 dependent differentiation fromfibroblast cells. Activation of theTGF-beta receptor 1 andTGF-beta receptor 2 leads to induction of the canonicalSMAD2/SMAD3 pathway.[3] Together with the co-activation of the non-canonicalEGFR pathway, these events lead to upregulation of theACTA2 gene and subsequent alpha smooth muscle actin protein production. Several regulators of the myofibroblast differentiation pathway have been described, includinghyaluronan andCD44 co-receptor activation of EGFR.[4]
In many organs like liver, lung, and kidneys, 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 renalmesangial cells are some examples of modified myofibroblast-like cells.
Myofibroblasts may interfere with the propagation of electrical signals[5] controlling heart rhythm,[6] leading toarrhythmia in both patients who have suffered a heart attack and in foetuses.Ursodiol is a promising drug for this condition.[7]
Myofibroblasts can contract by using smooth muscle type actin-myosin complex, rich in a form ofactin 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 thatgranulation tissue taken from a wound could contractin vitro (or in an organ bath) in a similar fashion to smooth muscle, when exposed to substances that cause smooth muscle to contract, such asadrenaline orangiotensin.
More recently it has been shown that fibroblasts can transform into myofibroblasts withphotobiomodulation.
After healing is complete, these cells are lost throughapoptosis and it has been suggested that in several fibrotic diseases (for exampleliver cirrhosis, kidney fibrosis, retroperitoneal fibrosis) that this mechanism fails to work, leading to persistence of the myofibroblasts, and consequently expansion of theextracellular matrix (fibrosis) with contraction.
Similarly, in wounds that fail to resolve and becomekeloids orhypertrophic scars, myofibroblasts may persist, rather than disappearing by apoptosis.[8]
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