Differences between Scar and Dermal Cultured Fibroblasts Derived from a Patient with Recurrent Abdominal Incision Wound Herniation

Abstract

Fibroblasts were derived from dermis and scar of a 47-year-old white man with a recurrent incisional hernia as a result of fractured ribs. The scar was thin and stretched, suggesting a defect in the maturation of granulation tissue. After surgical repair, biopsy specimens of discarded scar and skin were used to generate fibroblast cell lines. Fibroblasts maintained in medium containing 10% fetal bovine serum and antibiotic were studied between their third and eighth passage. By phase contrast microscopy, no structural differences were obvious, but it was noted that to pass scar fibroblasts, a more aggressive trypsin regimen was required. Immunohistologic and Western blot analysis of patient scar fibroblasts showed (1) more a smooth muscle actin within stress fibers, (2) increased expression of the vitronectin integrin receptor alpha(v) (CD 51), and (3) reduced expression of the collagen integrin receptor alpha2 (CD 49b). The expression of vinculin from focal adhesions or a tubulin from microtubules was the same among cell lines. Contractions of scar and dermal fibroblast-populated collagen lattice were compared. At 24 hours, contractions were 69 percent with newborn fibroblasts (normal); 68 percent for patient dermal fibroblasts; and only 48 percent for patient scar fibroblasts. The retarded contraction of scar fibroblast-populated collagen lattice was significant (p > or = 0.002). Myosin ATPase activity, critical for lattice contraction, and cell migration were equivalent among all cell lines. A plausible mechanism for the retardation of scar lattice contraction is disruption of fibroblasts and collagen interactions, for which the attachment of cells to collagen is altered. It is proposed that either the decrease in the expression of collagen integrin receptor alpha2 (CD 49b), an increase in the expression of the vitronectin receptor alpha(v) (CD 51), or a combination of both is responsible for disruption of collagen fibroblast interactions.

Fibroblast expression of α-smooth muscle actin, α2β1 integrin and αvβ3 integrin: Influence of surface rigidity

“…In the absence of tension, RPTPα cannot interact with the αvβ3 integrin at the cell’s periphery. Increasing αvβ1 expression reduces the rate and degree of free floating PCL contraction (Boemi et al, 1999; Lygoe et al, 2004). The αvβ3 integrin RPTPα complex senses mechanical tension at the leading edge of cells, passing on properties of the extracellular matrix to intracellular signal transduction pathways (Jiang et al, 2006).…”

Alpha V Integrin Prolongs Collagenase Production Through Jun Activation Binding Protein 1

“…Indeed, the etiology of a recurrent, thin, stretched-out scar of our patient can be attributed to ␣v-mediated MMP1 production through JAB1 signaling. 7 The correlation between ␣v integrin activation and MMP production is not novel. Expression of MMP2 (gelatinase a; type IV collagenase) and ␣v␤3 is associated with melanoma progression and osteopontin stimulation of smooth muscle cell ␣v␤3 increases MMP1 (interstitial collagenase) production.…”

“…Up-regulation of integrin receptor expression alone or a switch in integrin profiles is enough to trigger signaling events that alter normal wound healing. 7 ␣v Integrin is implicated in abnormal wound healing. To date, the mediators of ␣v integrin signaling are largely undefined, but JAB1 apparently interacts with the cytoplasmic tail of ␣v to regulate the signaling cascade.…”

“…In wound healing, ␣v␤3 overexpression enhances ECM organization, stimulates fibroblast migration, and leads to scar thinning. 7 Boemi et al 7 noted ␣v overexpression in dermal fibroblasts is associated with a patient's recurrent, thin, stretched-out scar.…”

Overexpression of integrin αv promotes human osteosarcoma cell populated collagen lattice contraction and cell migration

“…As well, the finding clarifies a potential mechanism for avb3 expressing melanoma and breast cancer cells metastasis and helps to solidify the understood relationship between invasiveness of cutaneous malignant melanoma and collagenase production (Nip et al, 1992;Sipkins et al, 1998;Wong et al, 1998;Ye et al, 2001). In addition, dermal fibroblasts that overexpress av integrin are associated with abnormal wound repair (Boemi et al, 1999). Clearly, av integrin has several important biological functions and, therefore, it is important to elucidate which ECM ligands av interacts with and how these av-ligand interactions are transmitted intracellularly.…”