A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen , produces the structural framework ( stroma ) for animal tissues , and plays a critical role in wound healing . Fibroblasts are the most common cells of connective tissue in animals.
27-421: IL-11 or IL 11 can refer to: Interleukin 11 Illinois's 11th congressional district Illinois Route 11 [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to
54-431: A branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli . Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum (RER). Inactive fibroblasts, called ' fibrocytes ', are smaller, spindle-shaped, and have less RER. Although disjointed and scattered when covering large spaces, fibroblasts often locally align in parallel clusters when crowded together. Unlike
81-633: A process called epithelial-mesenchymal transition . Conversely, fibroblasts in some situations may give rise to epithelia by undergoing a mesenchymal to epithelial transition and organizing into a condensed, polarized, laterally connected true epithelial sheet. This process is seen in many developmental situations (e.g. nephron and notocord development), as well as in wound healing and tumorigenesis. Fibroblasts make collagen fibers, glycosaminoglycans , reticular and elastic fibers . The fibroblasts of growing individuals divide and synthesize ground substance. Tissue damage stimulates fibrocytes and induces
108-621: A role during blastocyst implantation in the uteral endometrium ; as the blastocyst is imbedded within the endometrium, extravillous trophoblasts invade the maternal spiral arteries for stability and the transfer of life-sustaining elements via the maternal and fetal circulatory systems. This process is highly regulated due to detrimental consequences that can arise from aberrations of the placentation process: poor infiltration of trophoblasts may result in preeclampsia , while severely invasive trophoblasts may resolve in placenta accreta , increta or percreta; all defects that most likely would result in
135-447: Is a protein that in humans is encoded by the IL11 gene . IL-11 is a cytokine that was first isolated in 1990 from bone marrow -derived fibrocyte -like stromal cells . It was initially thought to be important for hematopoiesis , notably for megakaryocyte maturation, but subsequently shown to be redundant for platelets , and for other blood cell types, in both mice and humans. It
162-439: Is associated with a variety of cancers and may provide a link between inflammation and cancer. IL-11 has been demonstrated to improve platelet recovery after chemotherapy-induced thrombocytopenia , induce acute phase proteins , modulate antigen-antibody responses, participate in the regulation of bone cell proliferation and differentiation IL-11 causes bone-resorption. It stimulates the growth of certain lymphocytes and, in
189-464: Is important in wound healing . However dysregulation of TGFβ1 and downstream IL-11 is associated with fibrotic diseases hence inhibition of IL-11 may have utility in treating fibrosis. This cytokine promotes recruitment of immune suppressive cancer-associated fibroblasts to tumors and facilitates chemoresistance . It is also under investigation as a way to allow diabetes -damaged kidney tissue to regenerate. Fibroblasts Fibroblasts have
216-467: Is initiated upon binding of IL-11 to IL-11Rα and gp130 , facilitating the formation of higher order structures involving dimers of gp130:Il-11:Il11RA complexes. In some instances, in epithelial -derived cells and cancer cell lines, this permits gp130-associated Janus kinases (JAK) activation and downstream STAT-mediated transcriptional activities. In other instances, in stromal cells, IL-11 activates non-canonical MAPK /ERK-dependent signalling to initiate
243-536: Is manufactured using recombinant DNA technology. A recombinant form of IL-11, oprelvekin , is a protein therapeutic used for the prevention of severe thrombocytopenia in cancer patients. As IL-11 over-expression is associated with a number of cancers , inhibition of its signaling pathway may have utility in treating cancer, and has also been researched for its potential ability to slow down aging . Transforming growth factor β1 (TGFβ1) through up-regulation of IL-11, stimulates collagen production and
270-439: The epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina components in some situations (e.g. subepithelial myofibroblasts in intestine may secrete the α-2 chain-carrying component of the laminin , which is absent only in regions of follicle-associated epithelia which lack
297-621: The ground substance and a variety of fibers . The composition of the ECM determines the physical properties of connective tissues. Like other cells of connective tissue, fibroblasts are derived from primitive mesenchyme . Hence, they express the intermediate filament protein vimentin , a feature used as a marker to distinguish their mesodermal origin. However, this test is not specific as epithelial cells cultured in vitro on adherent substratum may also express vimentin after some time. In certain situations, epithelial cells can give rise to fibroblasts,
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#1732904905891324-484: The murine model, stimulates an increase in the cortical thickness and strength of long bones. In addition to having lymphopoietic/ hematopoietic and osteotrophic properties, it has functions in many other tissues, including the brain, gut, testis, kidney and bone. As a signaling molecule, interleukin 11 has a variety of functions associated with its receptor interleukin 11 receptor alpha; such functions include placentation and to some extent decidualization . IL11 has
351-479: The zebrafish or the axolotl . Here, activation of STAT3 by IL-11 is mandatory to allow regeneration and to prevent injury-induced fibrotic remodeling and scar formation. IL-11 through its binding to its transmembrane IL-11Rα receptor and resultant activation of downstream signaling pathways has been thought to regulate adipogenesis , osteoclastogenesis , neurogenesis and platelet maturation . More recently it has been discovered that over-expression of IL-11
378-408: The ECM remodeling. ECM remodeling is described as changes in the ECM as a result of enzyme activity which can lead to degradation of the ECM. Immune regulation of tumors is largely determined by ECM remodeling because the ECM is responsible for regulating a variety of functions, such as proliferation, differentiation, and morphogenesis of vital organs. In many tumor types, especially those related to
405-437: The body express many genes that code for immune mediators and proteins. These mediators of immune response enable the cellular communication with hematopoietic immune cells. The immune activity of non-hematopoietic cells, such as fibroblasts, is referred to as “structural immunity”. In order to facilitate a fast response to immunological challenges, fibroblasts encode crucial aspects of the structural cell immune response in
432-485: The development of clinical-grade products. In view of the potential clinical applications of stem cell-derived tissues or primary epithelial cells, the use of human fibroblasts as an alternative to MEF feeders has been studied. Whereas the fibroblasts are usually used to maintain pluripotency of the stem cells, they can also be used to facilitate development of the stem cells into specific type of cells such as cardiomyocytes. Fibroblasts from different anatomical sites in
459-544: The early demise of the embryo and/or negative effects upon the mother. IL11 is present in the decidua and chorionic villi to regulate the extent in which the placenta implants itself; regulations to ensure maternal well-being and the growth and survival of the fetus. A murine knockout model has been produced for this particular gene, with initial studies involving IL11 role in bone pathologies but have since progressed to fertility research; further research utilizes endometrial and gestational tissue from humans. Interleukin 11
486-543: The epithelial cells, ECM remodeling is common. Examples of TAF-derived ECM components include Tenascin and Thrombospondin-1 (TSP-1), which can be found in sites of chronic inflammation and carcinomas, respectively. Immune regulation of tumors can also occur through the TAF-derived modulators. Although these modulators may sound similar to the TAF-derived ECM components, they differ in the sense that they are responsible for
513-646: The intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IL-11&oldid=932888105 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Interleukin 11 4MHL 3589 16156 ENSG00000095752 ENSMUSG00000004371 P20809 P47873 NM_001267718 NM_000641 NM_008350 NM_001290423 NP_000632 NP_001254647 NP_001277352 NP_032376 Interleukin 11 (IL-11 or adipogenesis inhibitory factor )
540-514: The invasive microorganisms. Receptors on the surface of fibroblasts also allow regulation of hematopoietic cells and provide a pathway for immune cells to regulate fibroblasts. Fibroblasts, like tumor-associated host fibroblasts (TAF), play a crucial role in immune regulation through TAF-derived ECM components and modulators. TAF are known to be significant in the inflammatory response as well as immune suppression in tumors. TAF-derived ECM components cause alterations in ECM composition and initiate
567-417: The location and tissue context where they had previously resided, at least over a few generations. This remarkable behavior may lead to discomfort in the rare event that they stagnate there excessively. The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix (ECM), providing all such components, primarily
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#1732904905891594-403: The myofibroblast lining). Fibroblasts can also migrate slowly over substratum as individual cells, again in contrast to epithelial cells. While epithelial cells form the lining of body structures, fibroblasts and related connective tissues sculpt the "bulk" of an organism. The life span of a fibroblast, as measured in chick embryos, is 57 ± 3 days. Fibroblasts and fibrocytes are two states of
621-500: The post-transcriptional upregulation of specific subsets of transcripts in the absence of an effect on transcription. In fibroblasts, IL-11 drives an ERK-dependent autocrine loop of fibrogenic protein synthesis that is at a nexus of fibrotic signalling and required for the pro-fibrotic activity of TGFB1 , PDGF , endothelin1 , angiotensin and many other pro-fibrotic factors. IL-11 has also been described in various aspects of tissue regeneration, predominantly in regenerative species like
648-418: The production of fibroblasts. Besides their commonly known role as structural components, fibroblasts play a critical role in an immune response to a tissue injury. They are early players in initiating inflammation in the presence of invading microorganisms. They induce chemokine synthesis through the presentation of receptors on their surface. Immune cells then respond and initiate a cascade of events to clear
675-553: The same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. Currently, there is a tendency to call both forms fibroblasts. The suffix "-blast" is used in cellular biology to denote a stem cell or a cell in an activated state of metabolism . Fibroblasts are morphologically heterogeneous with diverse appearances depending on their location and activity. Though morphologically inconspicuous, ectopically transplanted fibroblasts can often retain positional memory of
702-584: The variation and turnover of the ECM. Cleaved ECM molecules can play a critical role in immune regulation. Proteases like matrix metalloproteineases and the uPA system are known to cleave the ECM. These proteases are derived from fibroblasts. Mouse embryonic fibroblasts (MEFs) are often used as supportive "feeder cells" in research using human embryonic stem cells, induced pluripotent stem cells and primary epithelial cell culture. However, many researchers are trying to phase out MEFs in favor of culture media with precisely defined ingredients in order to facilitate
729-722: Was developed as a recombinant protein (rhIL-11) as the drug substance oprelvekin . The human IL-11 gene , consisting of 5 exons and 4 introns , is located on chromosome 19 , and encodes a 23 kDa protein. IL-11 is a member of the IL-6 -type cytokine family, distinguished based on their use of the common co-receptor gp130 . Signal specificity is provided by the IL-11Rα subunit which is expressed at high levels in fibroblasts and other stromal cells but not immune cells, unlike IL6 receptors that are expressed at highest levels in immune cells and lowly expressed in stromal cells. Signal transduction
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