“…Several transcription factors are known to be important for the regulation of wound responses and regeneration [12, 76]. NF-κB factors are sensitive to redox state, and likely act downstream of early hydrogen peroxide signaling to stimulate inflammatory responses [77, 78].…”
Section: Discussionmentioning
confidence: 99%
“…NF-κB factors are sensitive to redox state, and likely act downstream of early hydrogen peroxide signaling to stimulate inflammatory responses [77, 78]. The basic-Helix-loop-Helix transcription factor Hypoxia-inducible factor 1 alpha ( HIF-1α ) is expressed at many injury sites following blood vessel changes [76]. Targeted disruption of HIF-1α in osteoblasts, keratinocytes, or Club cells results in impaired healing of bone or skin [79, 80], or asthma [81].…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, overexpression of Fra1 , a Fos family member that heterodimerizes with Jun proteins to form AP-1 [90], leads to impaired fracture healing that is thought to result from suppression of inflammation responses [91]. Kruppel-like and Grainy-head family transcription factors are expressed in injured epithelia and are required for establishment and repair of epithelial barrier functions [76, 92–95]. Following skin injury, KLF4-positive epidermal derivatives migrate into the junction between wounded and uninjured tissue [96], in a pattern very similar to Bmp5 IRE- lacZ expressing cells.…”
Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an “injury response” control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals.
“…Several transcription factors are known to be important for the regulation of wound responses and regeneration [12, 76]. NF-κB factors are sensitive to redox state, and likely act downstream of early hydrogen peroxide signaling to stimulate inflammatory responses [77, 78].…”
Section: Discussionmentioning
confidence: 99%
“…NF-κB factors are sensitive to redox state, and likely act downstream of early hydrogen peroxide signaling to stimulate inflammatory responses [77, 78]. The basic-Helix-loop-Helix transcription factor Hypoxia-inducible factor 1 alpha ( HIF-1α ) is expressed at many injury sites following blood vessel changes [76]. Targeted disruption of HIF-1α in osteoblasts, keratinocytes, or Club cells results in impaired healing of bone or skin [79, 80], or asthma [81].…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, overexpression of Fra1 , a Fos family member that heterodimerizes with Jun proteins to form AP-1 [90], leads to impaired fracture healing that is thought to result from suppression of inflammation responses [91]. Kruppel-like and Grainy-head family transcription factors are expressed in injured epithelia and are required for establishment and repair of epithelial barrier functions [76, 92–95]. Following skin injury, KLF4-positive epidermal derivatives migrate into the junction between wounded and uninjured tissue [96], in a pattern very similar to Bmp5 IRE- lacZ expressing cells.…”
Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an “injury response” control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals.
“…After human skin injury, wound healing occurs as a restorative process, divided into three overlapping phases: hemostasis/ inflammation, granulation tissue formation/re-epithelialization and tissue remodeling (Haertel et al, 2014;Wong et al, 2013). Human dermal fibroblasts (HDF) play a key role in this phenomenon by proliferating into the wound space, synthesizing extracellular matrix (ECM) components, developing mechanical forces and remodeling the scar (Singer and Clark, 1999).…”
“…Skin damage is generally associated with inflammation due to skin burns or inflammatory illness such as psoriasis, contactor atopic dermatitis, vulgaris acne, skin wounds, among others (Gittler et al 2013;Haertel et al, 2014;Kendall and Nicolaou, 2013;Wagener et al, 2013).…”
This study demonstrated for the first time the mechanisms involved in the topical anti-inflammatory effect presented by the semisolid containing A. moluccana dried extract pointing as the main mechanism is the reduction in the leukocyte migration and consequently resulting in diminished levels of cytokins and chemokines, indicating this herbal product as a promissor anti-inflammatory phytomedicine to treat skin inflammatory diseases.
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