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Connective Tissue Research 2014Cartilage is unique in being established as an avascular tissue during development. Cartilage also has the property of being resistant to tumor invasion with tumors... (Review)
Review
Cartilage is unique in being established as an avascular tissue during development. Cartilage also has the property of being resistant to tumor invasion with tumors arising on the periphery of cartilage and in bone, but sparing the cartilage. These properties have been investigated for many years beginning in the 1970's. Many anti-angiogenic molecules have been isolated from cartilage in small amounts. Portions of molecules from cartilage also possess anti-angiogenic properties when released from the parent protein by degradative extracellular enzymes. This review highlights a new anti-angiogenic and anti-tumor moiety from cartilage, the NH2-propeptide of type IIB collagen. When released from the procollagen during synthesis, the propeptide has the capacity to act on its own to protect the cartilage by killing of endothelial cell, osteoclasts and tumor cells.
Topics: Amino Acid Sequence; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Chondrocytes; Collagen Type II; Humans; Models, Biological; Molecular Sequence Data; Procollagen
PubMed: 24437601
DOI: 10.3109/03008207.2013.867340 -
Nihon Rinsho. Japanese Journal of... Feb 1995
Review
Topics: Adult; Collagen; Humans; Liver Diseases; Procollagen
PubMed: 8753399
DOI: No ID Found -
Clinical Biochemistry Aug 2012The aminoterminal propeptide of type I procollagen (PINP) in serum is a sensitive indicator of the synthesis of type I collagen. Four assays are available for PINP, two... (Review)
Review
The aminoterminal propeptide of type I procollagen (PINP) in serum is a sensitive indicator of the synthesis of type I collagen. Four assays are available for PINP, two of them (intact PINP assays) measure the intact propeptide and the other two (total PINP assays) also detect a smaller antigen in serum. In many clinical situations, these assays give similar information, but renal insufficiency increases the concentration of the smaller antigen, influencing both the apparent concentration of PINP and assay calibration. Serum PINP is mostly affected by changes in bone metabolism. In infants and children, the concentration is much higher than in adults. Serum PINP (s-PINP) is a useful indicator of disease activity in Paget's disease of bone, in bone metastases of osteoblastic nature, and in the follow-up of treatment of osteoporosis. The IFCC and IOF recently recommended the use of s-PINP as a reference marker for bone formation in studies concerning fracture risk assessment and treatment response.
Topics: Animals; Biomarkers; Blood Chemical Analysis; Chromatography, Gel; Collagen Type I; Humans; Immunoassay; Molecular Weight; Osteitis Deformans; Osteoporosis; Peptide Fragments; Procollagen
PubMed: 22480789
DOI: 10.1016/j.clinbiochem.2012.03.023 -
American Journal of Transplantation :... Mar 2023Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR...
Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.
Topics: Animals; Humans; Rats; Leukocytes, Mononuclear; Liver Transplantation; Macrophages; MicroRNAs; NF-kappa B; Procollagen
PubMed: 36695693
DOI: 10.1016/j.ajt.2022.12.009 -
Matrix Biology : Journal of the... Feb 1998As soon as procollagen precursors of fibrillar collagens were discovered in the early 1970s, it became apparent that connective tissues must contain proteolytic... (Review)
Review
Procollagen N-proteinase and procollagen C-proteinase. Two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling.
As soon as procollagen precursors of fibrillar collagens were discovered in the early 1970s, it became apparent that connective tissues must contain proteolytic activities that cleave the N-propeptides and the C-propeptides from procollagens. Isolation and characterization of the enzymic activities, however, proved to be unexpectedly difficult. Both proteinases are large and are synthesized in several different forms with polypeptide chains ranging in size from 70 kDa to about 130 kDa. The N-proteinase has the unusual property of cleaving the N-propeptides from type I and type II procollagens if the proteins are in a native conformation, but not if the proteins are partially unfolded so that the N-telopeptides are no longer in a hair-pin configuration. The C-proteinase specifically cleaves native and denatured types I, II and III procollagens. It also specifically cleaves a precursor of lysyl oxidase and laminin 5. Both enzymes and their variants have structures that place them in a large and expanding super-family of over 200 zinc-binding metalloproteinases. The larger of two forms of the N-proteinase contains an RGD sequence for binding through integrins and properdin repeats similar to those found in thrombospondin. The shorter 70 kDa form of the C-proteinase is identical to the protein that was previously identified as bone morphogenic protein-1. Both the 70 kDa C-proteinase and two larger forms are homologous to proteins that are expressed early in development in a variety of organisms, including Drosophila, sea urchin, and fish. Therefore, the data suggest that both the N- and C-proteinases have important biological functions in addition to the roles in the processing of procollagens.
Topics: Animals; Bone Morphogenetic Protein 1; Bone Morphogenetic Proteins; Humans; Metalloendopeptidases; Procollagen; Procollagen N-Endopeptidase; Signal Transduction
PubMed: 9524360
DOI: 10.1016/s0945-053x(98)90013-0 -
Molecular Biology of the Cell Mar 2022Collagen is the major protein component of the extracellular matrix. Synthesis of procollagens starts in the endoplasmic reticulum (ER), and three α chains form a rigid...
Collagen is the major protein component of the extracellular matrix. Synthesis of procollagens starts in the endoplasmic reticulum (ER), and three α chains form a rigid triple helix 300-400 nm in length. It remains unclear how such a large cargo is transported from the ER to the Golgi apparatus. In this study, to elucidate the intracellular transport of fibril-forming collagens, we fused cysteine-free GFP to the N-telopeptide region of procollagen III (GFP-COL3A1) and analyzed transport by live-cell imaging. We found that the maturation dynamics of procollagen III was largely different from that of network-forming procollagen IV. Proline hydroxylation of procollagen III uniquely triggered the formation of intralumenal droplet-like structures, similarly to events caused by liquid-liquid phase separation, and ER exit sites surrounded large droplets containing chaperones. Procollagen III was transported to the Golgi apparatus via vesicular and tubular carriers containing ERGIC53 and RAB1B; this process required TANGO1 and CUL3, which we previously reported to be dispensable for procollagen IV. GFP-COL3A1 and mCherry-α1AT were cotransported in the same vesicle. Based on these findings, we propose that shortly after ER exit, enlarged carriers containing procollagen III fuse to ERGIC for transport to the Golgi apparatus by conventional cargo carriers.
Topics: Biological Transport; Endoplasmic Reticulum; Golgi Apparatus; Procollagen; Protein Transport
PubMed: 35044867
DOI: 10.1091/mbc.E21-07-0372 -
Scandinavian Journal of Clinical and... 1997The biochemical possibilities for developing specific assays for type I collagen metabolism are described. Type I collagen synthesis can be assessed either by the... (Review)
Review
The biochemical possibilities for developing specific assays for type I collagen metabolism are described. Type I collagen synthesis can be assessed either by the analysis of the carboxyterminal or aminoterminal propeptides, which are in principle produced in a molar ratio of 1:1. However, in clinical situations altered behaviour can be found, the reasons for which may be altered clearance or even the existence of variant forms of type I collagen. Type I collagen degradation can be specifically detected by analysis of either cross-linked carboxy- or aminoterminal telopeptides or by the cross-links themselves liberated during the degradation processes. The heterogeneity of the cross-links and the constituent chains of the cross-linked peptides in different tissues and possibly in different clinical situations introduce problems, which should be studied and resolved in the future.
Topics: Biomarkers; Clinical Laboratory Techniques; Humans; Peptide Fragments; Procollagen
PubMed: 9127476
DOI: No ID Found -
Gastroenterology Jan 1990To localize the cellular sources of the collagens excessively deposited in the liver in the course of secondary biliary fibrosis, we have analyzed by in situ...
To localize the cellular sources of the collagens excessively deposited in the liver in the course of secondary biliary fibrosis, we have analyzed by in situ hybridization the distribution of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen and albumin RNA transcripts in rat livers up to 6 wk following common bile duct ligation and scission. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen RNA were found in nonparenchymal cells, while alpha 1(IV) procollagen gene expression was at the threshold of detection. Following bile duct obstruction, increasing amounts of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen gene transcripts were observed in cells of the expanding portal tracts and in perisinusoidal cells in areas of excessive collagen deposition. Procollagen gene expressing perisinusoidal cells were colocalized with desmin-immunoreactive cells, suggesting that Ito cells and transitional cells were among the collagen-expressing cell types. Only alpha 1(IV) procollagen transcripts were found in epithelial cells of newly formed bile ducts. Neither normal nor fibrotic liver showed any hybridization signal above background over hepatocytes, indicating that hepatocytes are unlikely to be a major source of hepatic collagen.
Topics: Animals; Cholestasis; Extracellular Matrix; Female; Gene Expression; Liver; Liver Cirrhosis, Experimental; Nucleic Acid Hybridization; Procollagen; RNA Probes; Rats; Transcription, Genetic
PubMed: 2293576
DOI: 10.1016/0016-5085(90)91307-r -
Nature Reviews. Disease Primers Jul 2020
Topics: Ehlers-Danlos Syndrome; Humans; Procollagen
PubMed: 32733050
DOI: 10.1038/s41572-020-0206-9 -
FEBS Letters Jan 2000In cells, only properly folded procollagen trimers are secreted from the endoplasmic reticulum (ER), while improperly folded abnormal procollagens are retained within...
In cells, only properly folded procollagen trimers are secreted from the endoplasmic reticulum (ER), while improperly folded abnormal procollagens are retained within the ER. Ascorbic acid is a co-factor in procollagen hydroxylation, which in turn is required for trimer formation. We examined chaperone proteins which bound to procollagen in the absence of ascorbic acid, a model which mimics the human disease scurvy at the cellular level. We found that both prolyl 4-hydroxylase (P4-H)/protein disulfide isomerase (PDI) and HSP47 bound to procollagen in the absence of ascorbic acid. However, the binding of PDI to procollagen decreased when HSP47 was co-transfected, suggesting that HSP47 and PDI compete for binding to procollagen. These data indicate that P4-H/PDI and HSP47 have cooperative but distinct chaperone functions during procollagen biosynthesis.
Topics: Animals; Ascorbic Acid; Cattle; Cell Line; Endoplasmic Reticulum; HSP47 Heat-Shock Proteins; Heat-Shock Proteins; Humans; In Vitro Techniques; Molecular Chaperones; Procollagen; Procollagen-Proline Dioxygenase; Protein Binding; Protein Biosynthesis; Protein Disulfide-Isomerases; Protein Structure, Quaternary; Rabbits; Transfection
PubMed: 10648804
DOI: 10.1016/s0014-5793(99)01713-5