title: Mechanisms of microvascular wound repair II. Injury induces transformation of endothelial cells into myofibroblasts and the synthesis of matrix proteins.
abstract: Under normal growth conditions, in vitro dermal microvascular endothelial cells (HDMEC) retain an epithelioid morphology and do not synthesize matrix proteins found increased in scar tissue. When injured by a standard scratch, cells at the wound edge and within the culture transform into spindle-shaped, myofibroblast-like cells. To determine if the transformed cells synthesize matrix proteins, expression of type I collagen and alpha smooth muscle actin (alpha-SMA) was investigated by immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Twelve hours following injury, a major upregulation in expression of alpha-SMA and type I collagen was observed both in cells proximal and distal to the wound edge. Cells with the typical morphology of myofibroblasts and displaying intracellular alpha-SMA positive fibrils were observed in HDMEC throughout the culture. In contrast, type IV collagen, a basement membrane protein, was not detected in migrating cells. Following completion of wound repair (24-36 h), type I collagen was no longer expressed and type IV collagen synthesis increased to prewound levels. Quantitative RT-PCR confirmed the changes in gene expression for both type I collagen and alpha-SMA at each time point during repair. These results demonstrate that normal skin microvascular endothelial cells retain an ability to transform into myofibroblast-like cells when injured and to synthesize matrix proteins not expressed in noninjured cells. The synthesis of matrix proteins by injured endothelial cells suggests a direct role for the endothelium in the pathology of scar formation.
authors.affiliation: Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Chaudhuri
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Karasek
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001808:Blood Vessels / Q000502:physiology*; D002461:Cell Line, Transformed; D048429:Cell Size; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000098:blood supply / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D013997:Time Factors; D014945:Wound Healing
chemical_list: D000199:Actins; D024042:Collagen Type I; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins