The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters
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The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters. / Nielsen, Mette J.; Nedergaard, Anders F.; Sun, Shu; Veidal, Sanne S.; Larsen, Lise; Zheng, Qinlong; Suetta, Charlotte; Henriksen, Kim; Christiansen, Claus; Karsdal, Morten A.; Leeming, Diana J.
I: American Journal of Translational Research, Bind 5, Nr. 3, 2013, s. 303-315.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters
AU - Nielsen, Mette J.
AU - Nedergaard, Anders F.
AU - Sun, Shu
AU - Veidal, Sanne S.
AU - Larsen, Lise
AU - Zheng, Qinlong
AU - Suetta, Charlotte
AU - Henriksen, Kim
AU - Christiansen, Claus
AU - Karsdal, Morten A.
AU - Leeming, Diana J.
PY - 2013
Y1 - 2013
N2 - Aim: The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3). Methods: The monoclonal antibody was raised against the N-protease mediated cleavage site of the N-terminal propeptide of type III collagen and a competitive ELISA was developed using the selected antibody. The assay was evaluated in relation to neo-epitope specificity, technical performance, and as a marker for liver fibrosis and muscle mass using the rat carbon tetrachloride (CCl4) model and a study of immobilization induced muscle loss in humans, respectively. Results: The ELISA was neo-epitope specific, technically stable and can be assessed in serum and plasma samples. In the CCl4 liver fibrosis model it was observed that serum PRO-C3 were significantly elevated in rats with liver fibrosis as seen by histology (56% elevated in the highest quartile of total hepatic collagen compared to control rats, p<0.001) and correlated significantly to total hepatic collagen in the diseased rats (r=0.46, p<0.01) and not in control rats, suggesting the pathological origin of the epitope. Human plasma PRO-C3 correlated significantly to muscle mass at baseline (R2=0.44, p=0.036). Conclusion: The developed neo-epitope specific serum ELISA for type III procollagen (PRO-C3) reflects true formation as it is specific for the propeptide cleaved off the intact collagen molecule. In a clinical and in a rodent study we showed that this marker was highly related to liver fibrosis and muscle mass.
AB - Aim: The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3). Methods: The monoclonal antibody was raised against the N-protease mediated cleavage site of the N-terminal propeptide of type III collagen and a competitive ELISA was developed using the selected antibody. The assay was evaluated in relation to neo-epitope specificity, technical performance, and as a marker for liver fibrosis and muscle mass using the rat carbon tetrachloride (CCl4) model and a study of immobilization induced muscle loss in humans, respectively. Results: The ELISA was neo-epitope specific, technically stable and can be assessed in serum and plasma samples. In the CCl4 liver fibrosis model it was observed that serum PRO-C3 were significantly elevated in rats with liver fibrosis as seen by histology (56% elevated in the highest quartile of total hepatic collagen compared to control rats, p<0.001) and correlated significantly to total hepatic collagen in the diseased rats (r=0.46, p<0.01) and not in control rats, suggesting the pathological origin of the epitope. Human plasma PRO-C3 correlated significantly to muscle mass at baseline (R2=0.44, p=0.036). Conclusion: The developed neo-epitope specific serum ELISA for type III procollagen (PRO-C3) reflects true formation as it is specific for the propeptide cleaved off the intact collagen molecule. In a clinical and in a rodent study we showed that this marker was highly related to liver fibrosis and muscle mass.
KW - Biochemical markers
KW - Formation
KW - Liver fibrosis
KW - Muscle mass
KW - Neo-epitope
KW - Type iii collagen
M3 - Journal article
AN - SCOPUS:84877014403
VL - 5
SP - 303
EP - 315
JO - American Journal of Translational Research
JF - American Journal of Translational Research
SN - 1943-8141
IS - 3
ER -
ID: 388029952