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Spatial and temporal expression of transforming growth factor-beta isoforms during ovine excisional and incisional wound repair.

To elucidate the role for transforming growth factor-beta isoforms (beta(1), -beta(2), and -beta(3)) in wound repair, we used isoform-specific antibodies to detect the spatial and temporal expression of the latent and mature/active transforming growth factor-beta isoforms by immunohistochemical localization through 21 days after excisional and incisional wounding of ovine skin. Although incisional and excisional wounds showed similar patterns of transforming growth factor-beta immunoreactivity, we found a differential temporal and spatial expression of the latent and mature transforming growth factor-beta isoforms throughout wound repair. Specifically, 1 day after wounding, there was a marked increase in transforming growth factor-beta isoforms in the epithelium adjacent to the wound, epidermal appendages, and the cells and matrix of the granulation tissue. At this time, transforming growth factor-beta(3) isoform was the most abundant. Most notably, the epidermis adjacent to the wound was intensely immunoreactive for all transforming growth factor-beta isoforms 1 day after injury. However, the migrating epithelium, derived from both the hair follicles and the wound margins, was completely devoid of immunoreactive transforming growth factor-beta until reepithelialization was complete. Within the inflammatory exudate, there was a distinct band of leukocytes that was immunoreactive for transforming growth factor-beta(2) and -beta(3) 1 day after injury and 1 day later for transforming growth factor-beta(1). Although transforming growth factor-beta(1) and -beta(2), latent transforming growth factor-beta(2), transforming growth factor-beta(3), and latent transforming growth factor-beta(3) immunostaining was present in the numerous fibroblasts and other dermal cells, latent transforming growth factor-beta(1) was only associated with the extracellular matrix. In general, immunoreactivity remained high until day 7 after wounding and slowly subsided over time. However, by day 21, immunostaining had not returned to normal and the original wound was replete with immunoreactive fibroblasts and a dense, immunostained extracellular matrix. Thus, although the dynamic presence of transforming growth factor-beta isoforms exemplifies its positive role in the wound repair process, its persistence together with its known potent effects on matrix accumulation, supports its role in scar formation.

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High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer.

Several genes have identified that play a role in colon cancer development. However, less is known about factors that increase the rate of progression of colon cancers to metastasis. One candidate is transforming growth factor beta 1 (TGF beta 1), which can enhance the aggressiveness of human colorectal cell lines in vitro and in vivo. The amount of TGF beta 1, TGF beta 2, and TGF beta 3 protein isoforms expressed in primary site colorectal cancers were measured to determine whether any correlation existed between protein levels and disease recurrence in a series of Memorial Sloan-Kettering Hospital patients who underwent potentially curative resections. Intense staining for TGF beta 1 correlated significantly (P < 0.0013; odds ratio, 18) with disease progression to metastasis and was independent of nodal status and the degree of differentiation of the primary tumor. Therefore, in this study, patients with high TGF beta 1 protein levels in their primary site colorectal cancer were 18 times more likely to experience recurrence of their disease than were patients whose tumors exhibited low levels of TGF beta 1. In this case-control study, patients whose cancer recurred and those remaining cancer free were age and sex matched. The disease recurred at a mean of 26.8 +/- 4.3 (SE) months, whereas the mean follow-up time in patients whose disease did not recur was over twice as long, 57.3 +/- 6.6 months. Ninety-four % of the patients in each group were node positive at the time of resection, with equal mean numbers of positive nodes per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

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