A 27-year-old woman comes to the emergency department with a scalp laceration after a fall. She reports a tendency to develop big scars even with small injuries. Physical examination reveals an old, healed laceration as shown in the image below. Histochemical analysis of her tissue reveals fibroblasts that overexpress a cytokine essential for normal wound healing. Which of the following substances is most likely involved?

Question

A 27-year-old woman comes to the emergency department with a scalp laceration after a fall.  She reports a tendency to develop big scars even with small injuries.  Physical examination reveals an old, healed laceration as shown in the image below.  Histochemical analysis of her tissue reveals fibroblasts that overexpress a cytokine essential for normal wound healing.  Which of the following substances is most likely involved?

Quizplus · Accepted Answer

Wound healing generally proceeds in 3 phases: The inflammatory phase begins with formation of a fibrin clot that results in hemostasis. Cytokines released by activated platelets and damaged cells lead to migration of neutrophils (within the first 24 hours) and macrophages (2-3 days later) to the damaged area. The proliferative phase begins 3-5 days after the injury. Fibroblasts and endothelial vascular cells proliferate to form connective tissue and blood vessels (neovascularization), respectively. Around this time, epithelial cells begin to proliferate at the dermal edges and secrete basement membrane material. The maturation phase is characterized by fibrosis (scar formation) and starts during the second week after injury. During this phase, active fibroblasts synthesize collagen, elastin, and other components of the connective tissue matrix. During the healing process, fibroblast migration and proliferation are controlled by multiple growth factors including platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β). TGF-β is also critical for stimulating connective tissue synthesis and remodeling of the extracellular matrix. TGF-β typically decreases during the maturation phase of wound healing to limit the amount of collagenous scar tissue. Hypertrophic or disfiguring scars can be caused by persistently elevated TGF-β, which leads to increased fibroblast proliferation and activity. In addition, the fibroblasts in hypertrophic scars often have altered TGF-β signaling due to increased TGF-β receptor expression. (Choice A) Interferon-β is an antiviral cytokine that also decreases inflammatory cell movement across the blood-brain barrier. Interferon-β analogs can be used to treat multiple sclerosis. (Choice B) Interleukin-17 (IL-17) is produced by T_H17 cells and recruits neutrophils in addition to stimulating production of antimicrobial peptides. IL-17 improves host defense against fungi and bacteria at epithelial and mucosal surfaces. Dysregulation has been implicated in many autoimmune conditions. (Choice C) Nuclear factor-kappa B (NF-κB) is a proinflammatory transcription factor that regulates cytokine production, adhesion molecule expression, and cell survival. Increased NF-κB activity is found in many cancers and inflammatory diseases (eg, rheumatoid arthritis, inflammatory bowel disease). (Choice E) Tumor necrosis factor-α (TNF-α) is a cytokine secreted by activated macrophages and T cells that promotes leukocyte recruitment, induces the systemic inflammatory response (eg, fever, acute-phase proteins), and regulates apoptosis. Educational objective: Transforming growth factor-β (TGF-β) is critical for fibroblast migration, proliferation, and connective tissue synthesis. Increased TGF-β activity is responsible for the hypertrophic/keloid scarring and fibrosis of the lung, liver, and kidney that occur with chronic inflammation. __________ References: The role of the TGF-ß family in wound healing, burns and scarring: a review (http://www.ncbi.nlm.nih.gov/pubmed/22928164)

A 27-Year-Old Woman Comes to the Emergency Department with a Scalp