Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis

Leeming, Diana Julie; Veidal, Sanne Skovgård; Karsdal, Morten A.; Nielsen, Mette Juul; Trebicka, Jonel; Busk, Troels M.; Bendtsen, Flemming; Krag, Aleksander; Möller, Sören

doi:10.3109/00365521.2014.996590

Cited by 44 publications

(29 citation statements)

References 34 publications

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“…The serological biomarkers of interstitial matrix turnover were assessed by type 3, 5, and 6 collagen formation (PRO‐C3, N‐terminal propeptide of type 5 procollagen [PRO‐C5], and N‐terminal propeptide of type 6 procollagen [PRO‐C6]), and type 3 collagen degradation was assessed by matrix metallopeptidase 9 (C3M). Basement membrane formation was evaluated by type 4 collagen formation (P4NP7S) and type 4 collagen degradation mediated by matrix metallopeptidases (C4M2).…”

Section: Methodsmentioning

confidence: 99%

Collagen Formation Assessed by N‐Terminal Propeptide of Type 3 Procollagen Is a Heritable Trait and Is Associated With Liver Fibrosis Assessed by Magnetic Resonance Elastography

et al. 2019

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N‐terminal propeptide of type 3 procollagen (PRO‐C3) is a biomarker of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). This study examines the association between PRO‐C3 concentration and liver fibrosis assessed by magnetic resonance elastography (MRE)–measured stiffness (MRE‐stiffness) and the heritability of PRO‐C3 concentration in a cohort of twins and families with and without NAFLD. We performed a cross‐sectional analysis of a well‐characterized prospective cohort of 306 participants, including 44 probands with NAFLD‐cirrhosis and their 72 first‐degree relatives, 24 probands with NAFLD without advanced fibrosis and their 24 first‐degree relatives, and 72 controls without NAFLD and their 72 first‐degree relatives. Liver steatosis was assessed by magnetic resonance imaging proton density fat fraction, and liver fibrosis was assessed by MRE‐stiffness. Serum PRO‐C3 was assessed by competitive, enzyme‐linked immunosorbent assay. We assessed the familial correlation of PRO‐C3 concentration, the shared gene effects between PRO‐C3 concentration and liver steatosis and fibrosis, and the association between PRO‐C3 concentration and genetic variants in the patatin‐like phospholipase domain–containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane‐bound O‐acyltransferase domain–containing (MBOAT), and glucokinase regulator (CGKR) genes. In multivariable‐adjusted models including age, sex, body mass index, and ethnicity, serum PRO‐C3 correlated strongly with liver fibrosis (r2 = 0.50, P < 0.001) and demonstrated robust heritability (h2, 0.36; 95% confidence interval [CI], 0.07, 0.59; P = 0.016). PRO‐C3 concentration and steatosis had a strong genetic correlation (shared genetic determination: 0.62; 95% CI, 0.236, 1.001; P = 0.002), whereas PRO‐C3 concentration and fibrosis had a strong environmental correlation (shared environmental determination: 0.55; 95% CI, 0.317, 0.717; P < 0.001). PRO‐C3 concentrations were higher in carriers of the TM6SF2 rs58542926‐T allele compared with noncarriers: 15.7 (± 10.5) versus 10.8 (± 5.7) ng/L (P = 0.047). Conclusion: Serum PRO‐C3 correlates with MRE‐assessed fibrosis, is heritable, shares genetic correlation with liver steatosis and shares environmental correlation with liver fibrosis. PRO‐C3 concentration appears to be linked to both fibrosis and steatosis and increased in carriers of the TM6SF2 rs58542926 risk allele.

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Section: Methodsmentioning

confidence: 99%

Collagen Formation Assessed by N‐Terminal Propeptide of Type 3 Procollagen Is a Heritable Trait and Is Associated With Liver Fibrosis Assessed by Magnetic Resonance Elastography

et al. 2019

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“…We used validated competitive ELISAs (Nordic Bioscience, Herlev, Denmark) to assess true formation of interstitial matrix collagen type III and V (PRO‐C3 and PRO‐C5) and degradation of interstitial matrix collagen type III and basement membrane type IV collagen (C3M and C4M) in serum samples from PSC to ulcerative colitis patients. All biomarkers were assessed in a blinded manner according to the manufacturer and samples were measured within the detection range.…”

Section: Methodsmentioning

confidence: 99%

Serological markers of extracellular matrix remodeling predict transplant‐free survival in primary sclerosing cholangitis

Nielsen¹,

Thorburn²,

Leeming³

et al. 2018

Aliment Pharmacol Ther

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“…The interstitial ECM in fibrosis mainly consists of fibril‐forming type I and type III, and minor quantities of type V collagen. Type V collagen regulates fibril size, whereas types I and III are mainly structural. The precursors of these collagens consist of a large central triple helical region, with N‐ and C‐terminal propeptides covalently linked to each end.…”

Section: How Are Collagen Biomarkers Generated?mentioning

confidence: 99%

Collagen biology and non‐invasive biomarkers of liver fibrosis

Karsdal

Daniels

Nielsen

et al. 2020

Liver International

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113

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There is an unmet need for high‐quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non‐alcoholic fatty liver disease (NAFLD). In particular, there is a need for diagnostic and prognostic tools, as well as predictive biomarkers that reflect the efficacy of interventions, as described by the BEST criteria (Biomarkers, EndpointS, and other Tools Resource). This review covers the various liver collagens, their functional role in tissue homeostasis and delineates the common nomenclature for biomarkers based on BEST criteria. It addresses the common confounders affecting serological biomarkers, and describes defined collagen epitope biomarkers that originate from the dynamic processes of extracellular matrix (ECM) remodelling during liver injury.

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Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis

Cited by 44 publications

References 34 publications

Collagen Formation Assessed by N‐Terminal Propeptide of Type 3 Procollagen Is a Heritable Trait and Is Associated With Liver Fibrosis Assessed by Magnetic Resonance Elastography

Collagen Formation Assessed by N‐Terminal Propeptide of Type 3 Procollagen Is a Heritable Trait and Is Associated With Liver Fibrosis Assessed by Magnetic Resonance Elastography

Serological markers of extracellular matrix remodeling predict transplant‐free survival in primary sclerosing cholangitis

Collagen biology and non‐invasive biomarkers of liver fibrosis

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