Circulating levels of a collagen type v propeptide fragment in a carbon tetrachloride reversible model of liver fibrosis

四氯化碳可逆性肝纤维化模型中胶原蛋白 V 型前肽片段的循环水平

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作者:E Vassiliadis, S S Veidal, C Hansen, M A Karsdal, D J Leeming

Aim

To measure levels of the collagen V formation marker CO5-1230 during liver fibrosis progression and regression.

Conclusions

The data indicates that CO5-1230 levels are statistically significantly increased when CCl(4) intoxication stimulus is applied in all treatment time points. CO5-1230 levels return back to control levels when the stimulus is removed. The above finding adds to our previous evaluation of the marker and suggests that CO5-1230 may be a promising potential marker for liver fibrosis staging and monitoring in both disease progression and regression.

Methods

Monoclonal antibodies were raised against the sequence TAALGDIMGH located at the start of the C-terminal propeptide between amino acid position 1230' and 1239' (CO5-1230). An assay developed using the biotin-streptavidin system was evaluated in a rat reversible model of fibrosis. Animals were treated for duration of 4, 6 and 8 weeks. Animals that were treated for 8 weeks were left to regress for a period of 14, 20 and 26 weeks.

Results

Mean CO5-1230 level for control animals was found to be 8.7 ng/mL. CO5-1230 marker levels, at termination points, for CCl(4) treated animals was be 8.7 ng/mL at 4 weeks (P < 0.05, ROC: 0.83), 11.4 ng/mL at 6 weeks (P < 0.001, ROC: 0.93) and 10.8 ng/mL at 8 weeks (P < 0.05, ROC: 0.82). During regression phase, marker levels were statistically significantly decreased when compared with the marker levels at 8 weeks of treatment. Marker levels were found to be 5.9 ng/mL (P < 0.001, ROC: 0.8) after 14 weeks of regression, 3.9 ng/mL (P < 0.001, ROC: 0.95) after 20 weeks and 4.5 ng/mL (P < 0.001, ROC: 0.97) after 26 weeks of regression. Conclusions: The data indicates that CO5-1230 levels are statistically significantly increased when CCl(4) intoxication stimulus is applied in all treatment time points. CO5-1230 levels return back to control levels when the stimulus is removed. The above finding adds to our previous evaluation of the marker and suggests that CO5-1230 may be a promising potential marker for liver fibrosis staging and monitoring in both disease progression and regression.

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