Fibroblasts from non-healing human chronic wounds show decreased expression of βig-h3, a TGF-β inducible protein

SummaryBackgroundIncreasing evidence shows persistent phenotypic alterations in fibroblasts from non-healing human chronic wounds, which may result in faulty extracellular matrix deposition and keratinocyte migration. We have previously shown that these cells are characterized by morphological changes, low proliferative potential and unresponsiveness to TGF-β1, and down regulated phosphorylation of Smad 2/3 and p42/44 MAPK from decreased expression of the TGF-β type II receptor.ObjectiveTo identify genes and proteins that may be differentially expressed in chronic wounds and their cultured fibroblasts.MethodsDifferential display analysis with 120 random primer sets was used in fibroblasts from human venous ulcers and acute wounds created on the ipsilateral thighs of the same patients. Positive differential results were confirmed by RT-PCR. Immunohistochemistry of cultured fibroblasts and tissues was used to determine the expression of differentially expressed proteins.ResultsA total of 16 differentially expressed genes were identified and cloned. The only candidate gene that was differentially expressed in all patients and confirmed by repeated differential display testing and RT-PCR was βig-h3, a TGF-β-induced gene involved in cell adhesion, migration, and proliferation. Decreased expression of βig-h3 in chronic wounds and their fibroblasts was further confirmed by Western blot and immunostaining.ConclusionThese findings point to βig-h3 as an important gene characterizing the abnormal phenotype of chronic wound fibroblasts. Corrective measures to increase the expression of this protein might have therapeutic potential.