Tenascin-C promotes the proliferation and fibrosis of mesangial cells in diabetic nephropathy through the ß-catenin pathway.

OBJECTIVE: To mechanistically assess the involvement of tenascin-C (TNC) in diabetic nephropathy (DN). METHODS: Renal specimens from DN patients were histopathologically examined, and their TNC expression patterns were evaluated via immunohistochemistry. Additionally, the hereditarily diabetic C57BL/KsJ db/db mice were induced to develop DN via adaptive feeding, and then their renal levels of TNC and ß-catenin were assessed via western blotting and immunohistochemistry. Furthermore, the TNC and ß-catenin levels in primary rat mesangial cells (RMCs) cultured with high glucose levels were assessed via western blotting. In parallel, RMCs cultured with TNC in the presence or absence of the ß-catenin blocker ICG-001 were analyzed for their fibronectin and collagen I levels via immunostaining, and for their fibronectin, α-SMA, vimentin, PDGFR-ß, PCNA, and ß-catenin levels via western blotting. RESULTS: The TNC levels in the specimens were associated with the pathological classification. In these DN specimens, TNC protein was highly detected in the MCs and slightly in the tubulointerstitium. Renal TNC (P < 0.05) and ß-catenin (P < 0.001) were upregulated in db/db vs. db/m mice. High-glucose treatment upregulated TNC (P < 0.01) and ß-catenin (P < 0.05) in RMCs. TNC treatment upregulated fibronectin (P < 0.05), α-SMA (P < 0.01), vimentin (P < 0.05), PCNA (P < 0.05), and ß-catenin (P < 0.05) in RMCs, as assessed via western blotting. Immunohistochemical analysis confirmed the fibronectin upregulation and showed collagen I upregulation. Western-blot results also showed that levels of fibronectin (P < 0.001), α-SMA (P < 0.01), vimentin (P < 0.001), PCNA (P < 0.05), PDGFR-ß (P < 0.05), and ß-catenin (P < 0.01) were lower in RMCs co-treated with TNC and ICG-001 than in TNC-treated cells. Immunofluorescence analysis confirmed the decreased fibronectin level and showed that the collagen I level was also decreased by ICG-001. CONCLUSION: TNC is upregulated in DN and induces MC proliferation and fibrosis through the ß-catenin pathway.

A survey on health effects in a human population exposed to permanent-waving solution containing thioglycolic acid.

Thioglycolic acid (TGA) is the active ingredient of permanent-waving solution (PWS). TGA has been shown to be a chemical of high toxicity, which can be absorbed through intact skin and cause damage to organs or systems in animals. This study evaluated the effect of TGA-containing PWS on the health of a human population in 3 substudies. Firstly, 57 female hairdressers exposed to TGA-containing PWS (cases) and 64 female schoolteachers (controls) were studied. Their menstruation state was evaluated with information obtained from interviews. The results revealed that the menoxenia rate in the cases was significantly higher than that in the controls (22.81% vs 9.38%, p<0.05). Secondly, 8 female hairdressers selected from those that participated in the above survey underwent a fluctuation test for the mutagenic activity of urine. Eight female medical students were chosen as controls. Difference in the mutagenic activity of urine on TA100 between the two groups was highly significant (110.30 +/- 45.95 vs 28.43 +/- 19.33, p<0.01). Finally, a micronucleus assay was carried out on scalp hair follicle cells in healthy volunteers. Scalp hair with the follicle cell mass was sampled from 8 male and 8 female volunteers before permanent waving and at 24, 48 and 72 h after waving. One thousand hair follicle cells were examined by light microscopy. The number of cells containing a micronucleus and the number of micronuclei in each cell was determined. The permillages of micronuclei in hair follicle cells before and after permanent waving were compared. Micronuclei presence reached its peak value (12.44) 24 h after permanent waving, which was significantly higher than that before waving (3.13, p<0.001). The rate decreased progressively after 24 h. Our results suggest that the reproductive function of hairdressers may be affected by long-term exposure to PWS, probably due to the presence of TGA, and more attention should be paid to its potential carcinogenic effects.