Differential Expression of TGF-в Isoforms in Human Kerationocytes by Narrow Band UVB: DISCUSSION

TGFs are potent multifunctional autocrine- and paracrine-acting regulators of morphogenesis, angio- genesis, adhesion, chemotaxis, immune response, and extracellular matrix formation. TGF-в plays an important role not only in cell growth control but also in inflammation and immunoregulation. Furthermore, TGF- в affects extracellular matrices by inducing the synthesis and secretion of many extracellular matrix proteins, increasing the expres¬sion of many integrins, and regulating the synthetic activity of secreted proteases and protease inhi- bitors. Exogenous TGF- в 1 has induced differentiation and apoptosis of normal proliferating human oral keratinocyte. In addition, pretreat- ment with TGF- в 1 enhanced UV-mediated c-Jun amino-terminal kinase activation, which is involved in UV-mediated apoptosis in a spontaneously im¬mortalized human keratinocyte cell line (HaCaT).

There are at least five different isoforms of TGF- в . These isoforms have been shown to be differen-tially expressed spatially and temporally in vivo throughout embryogenesis, tissue repair, and carcinogenesis, suggesting distinct roles for the individual isoforms in vivo. Recent studies have revealed different functions for each TGF-в iso- form in keratinocyte proliferation and differentiation. For example, TGF- в 1 was localized to the upper differentiated layers, the stratum granulosum and corneum, whereas TGF- в 2 and weaker TGF- в 3 immunostaining was present in all suprabasal layers of normal keratinizing epithelium. Different iso¬forms of TGF- в are also associated with different proliferation or differentiation states of the epidermis.
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Our results showed that TGF- в 1 mRNA and protein levels were increased after 48 hrs of NBUVB at 800, 1,000 and 1,200 mJ/cm2. The increased expression was in proportion to the irradiating NBUVB dose. Therefore, it may be suggested that the mechanism of treatment of NBUVB take place through induced differentiation of epidermal kerati- nocyte due to increased TGF-в1.

TGF- в 1 mRNA levels were increased and TGF- в 1 protein levels were decreased after 24 hr, but both increased after 48 hrs. These results were consistent with a study that reported cell growth arrest approximately 52 hrs after treatment with TGF- в . The discrepancies between relative mRNA and protein expression patterns suggest the possibility of post-transcriptional regulation of TGF- в 1 expression in selected cells or tissues.

Concentration of TGF-в 2 in psoriasis-related studies were a similar level to those in a normal person. There was no correlation between PASI (Psoriasis Area and Severity Index) and plasma TGF- в2, which can be explained by the predo-minant expression of TGF- в 2 in the lower epi-dermal layer. However, decreased TGF-в 2 has been shown to be associated with excessive proliferation of keratinocytes and increased risk of psoriasis in normal epidermis, which implicates the role of TGF- в 2 in skin proliferation and differentiation. Compared with normal skin, psoriatic skin lesions showed decreased TGF-в 2 staining in the epidermis, especially in the middle and lower epidermis. This suggests that the decrease of TGF- в 2 in the epi¬dermis of psoriatic skin may contribute to epidermal hyperplasia, a hallmark of psoriasis. In this study, TGF-в 2 mRNA levels were decreased at 800, 1,000 and 1,200 mJ/cm2 compared with the control group at 24 hr and 48 hr. The decrease was inversely proportional compared to TGF- в 1 with respect to both dose and time. Thus, we propose opposing roles for TGF- в 1 and TGF- в 2. In keratinocytes, TGF- в 1 contributes to delayed re-epithelialization and increased keratinocyte proliferation, while TGF- в2 has little effect on any parameters of repair, and exogenous TGF- в 3 has little effect on re-epithelia- lization. In fibroblasts, some studies report the opposing roles of TGF- в 1 to TGF- в3 and TGF- в 1 to TGF-в2. In mice with encephalomyelitis, there was an inverse relationship between expression of TGF- в 1 that is enhanced in mice with ence¬phalomyelitis, and TGF^3 that is enhanced in E2-protected mice. The TGF- в 3 isoform displayed anti-proliferative properties towards encephalitogenic cells in vitro. Thus, TGF- в 1 and TGF- в 3 isoforms were suggested to play opposing roles. In our study, we could not measure the protein levels of TGF- в3, and the mRNA levels of TGFb3 were increased at 24 hr. Therefore, it was unclear if TGF-в1 played an opposite role to TGFb3. However, because the mRNA levels of TGF- в 3 were increased at 24 hr and similar levels were seen at 48 hr, it can be assumed that TGF- в 3 is inhibited through autoregulation and that it functions opposite to TGF- в 2. cialis super active

Our results suggest a possible role for TGF- в 1 after NBUVB irradiation and opposing roles for TGF-в1 and TGF-в 2 isoforms in NBUVB irradia¬tion. Further evaluation is needed in order to clarify functions of TGF- в isoforms.

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Tags: NBUVB, Transforming growth factor в (TGF- в)

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