Enzyme‐linked immunosorbent serum assay specific for the 7S domain of Collagen Type IV (P4NP 7S): A marker related to the extracellular matrix remodeling during liver fibrogenesis

Abstract

This newly developed serum assay specific for P4NP 7S was highly related to liver fibrosis and correlated to extent of hepatic fibrosis. This assay may improve fibrosis quantification.

Extracellular Matrix Remodeling: The Common Denominator in Connective Tissue DiseasesPossibilities for Evaluation and Current Understanding of the Matrix as More Than a Passive Architecture, but a Key Player in Tissue Failure

“…195 Neoepitopes of these proteins may serve as valuable markers of liver ECMR. Promising candidates have been reported, including those derived from type IV collagen, 196,197 type I collagen, 198 type V collagen, 199 and type VI collagen. 200 Systemic approaches, such as global profiling of serum glycoproteins, have also been utilized, 201 and this technique is now being validated in rodent models (e.g., Fang et al, 202 Blomme et al,…”

“…A range of serological assessments have been developed to investigate some of the key structural proteins of the ECM (Table 3). 56,60,129,144,[196][197][198][199][200]217,274,276,278,311,314,[331][332][333][334][335][336][337][338][339][340][341][342][343][344][345][346][347] Measurement of these proteins may provide key information in clinical settings on the tissue turnover profile, and thereby assists in patient diagnosis, in identification of those patients in most need of treatment, and finally, in monitoring of clinical efficacy of interventions. These technologies may also be used in preclinical settings, in ex vivo and in vitro cultures, to determine the molecular mode of action in the assembly and maintenance of the matrix.…”

“…atherosclerosis (type I and III collagens, titin and versican) 217 . various fibrotic diseases including liver (type I, III, IV, V, VI collagens and biglycan), [59][60][61]144,196,197,199,200,218 lung (elastin, type I, III, and V collagen), 74,[220][221][222][223][224][225][226][227][228][229][230][231][232] and kidney. 233 Key lessons on the importance of the structural components of the matrix may be harvested from the genetic mutations that lead to pathologies.…”

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

“…They can be measured with protein fingerprint technology using specific antibodies 7. The levels of these ECM markers depend on the degree of fibrosis4, 8, 9, 10 and also reflect antifibrotic therapy 5, 11. Degradation markers and collagen type III formation, in particular, mirror progression of fibrosis and diagnosis of portal hypertension4, 10, 12, 13; however, the roles of these markers in decompensation of liver cirrhosis have not been assessed.…”

Serum Immunoreactive Collagen IV detected by Monoclonal Antibodies as a Marker of Severe Fibrosis in Patients with Non- Alcoholic Fatty Liver Disease

“…Assessment of basement membrane remodeling using monoclonal antibodies against neo-epitopes released in serum after the degradation of type IV collagen by matrix metalloproteinase has recently become possible. As novel markers of fibrosis, the serum levels of specific fragments of type IV collagen have been measured by competitive ELISAs [29][30][31]. These fibrosis markers are theoretically more reliable than others, because fibrosis is characterized by excessive basement membrane remodeling; furthermore, remodeling by matrix metalloproteinase generates neo-epitopes released into the circulation.…”