Pregnancy-Related Proteins Detected by Their Biological Activities
Gábor N. Than, Hans Bohn, Dénes G. Szabó in Advances in Pregnancy-Related Protein Research, 2020
Type IV collagen differs from other collagens (type I, II, and III) in that it contains very high levels of the hydroxylated amino acids, hydroxyproline, and hydroxylysin, with about 10% of the hydroxyproline existing as 3-hydroxyproline.228 Another type of collagen has been extracted from placenta which had an amino acid composition similar to type IV collagen except that it contained no cysteine but contained 3-hydroxyproline, low arginine, and alanine.229 This collagen was designated as type V collagen. Immunofluorescence studies with antibodies to type V collagen confirmed that this collagen is present in the trophoblast basement membrane in placenta.230 Another unique collagen fraction which was found to be rich in cysteine has been isolated from limited pepsin digests of human placental tissues by Furuto and Miller.231 Similar peptides were extracted by Jander et al.232 These fractions could be isolated mainly from the maternal villi of placenta, only small amounts being obtained from fetal chorionic villi and the fetal membranes of the amnion and chorion.
Composition of the Extracellular Matrix in Human Gliomas
Róza Ádány in Tumor Matrix Biology, 2017
Malignantly transformed cells can trigger different host cells and modulate their synthetic activity both qualitatively and quantitatively. Studies performed in vivo have indicated that mature human glial and neuronal cells do not express fibronectin or laminin intracellularly.18,19 In contrast in human gliomas, the arteries, veins, capillaries, and hyperplastic vascular glomeruloid structures have been found to stain intensely with anti-human fibronectin18,19 and anti-human laminin13 sera. Fibronectin expression in meningioma seems to be more complex since this antigen has been described both in the meningiomatous cells20 and in the matrix surrounding these cells.49 Type V collagen has been shown associated with some basement membranes or with such cells as epithelial or smooth muscle cells,15 while types I and III collagens are restricted to the fibrillar intercellular network of the vessel walls and connective tissue.5,8,10 The expression of the GMEM antigens by both neoplastic glial cells and hyperplastic mesenchymal cells was demonstrated in contrast with the expression of fibronectin and laminin by mesenchymal elements only.35
Collagen Types: Structure, Distribution, and Functions
Marcel E. Nimni in Collagen, 1988
This mode of chain assembly and propagation of triple-helical conformation produces asymmetric molecules in which the structural features are disposed in a manner reflecting the primary structure of the individual pro-α chains. By way of illustration, Figure 2A depicts a procollagen molecule of the fiber-forming collagens. It is composed of three chains with structural features shown in Figure 1A. As such, the native procollagen molecule contains a globular domain at each end of a lengthy triple-helical region. The latter region is interrupted for a short span at a single site in the N-terminal portion of the molecule. As also shown in Figure 2, extracellular processing of the fiber-forming procollagens may result in the elimination of virtually all elements of tertiary structure (Figure 2B) or may result in retention of the N-terminal propeptide sequences (Figure 2C). Current evidence indicates that extracellular processing of type I and II procollagens leads to eventual removal of the propeptide sequences from both ends of the molecules, while a substantial proportion of type III molecules retain their N-terminal propeptide sequences.2 Present data also suggest that extracellular processing of type V procollagen molecules results in the production of molecular species in which, similar to type III, the N-terminal propeptide sequences are retained.39 Further data, however, with respect to the disposition of structural features in the chains of type V collagen will be required to clarify this point.
Shedding light on developmental drugs for idiopathic pulmonary fibrosis
Published in Expert Opinion on Investigational Drugs, 2020
Paolo Spagnolo, Francesco Bonella, Christopher J Ryerson, Argyris Tzouvelekis, Toby M Maher
Type V collagen (Col V) is a regulatory fibril-forming collagen of the extracellular matrix that is found primarily within the fibrils of the major lung collagen type I. Col V interacts with matrix collagens and structural proteins to confer and preserve elasticity and structural integrity to the lung parenchyma [48]. Despite being a native protein, Col V may act as a ‘foreign antigen’ if exposed following lung injury, leading to an autoimmune response as shown in human and rodent studies of lung transplantation [49]. Levels of Col V are increased in lung biopsies of patients with IPF [50], and Col V–induced tolerance abrogates fibrogenesis and down-regulates TGF-β-related signaling pathways in the bleomycin model of pulmonary fibrosis [51]. A phase 1, open-label study was designed to assess the safety, tolerability, and biological and clinical effects of three different doses (0.1, 0.5 and 1 mg/day) of IW001, a Col V oral immunotherapy, in anti-Col V Ab+ patients with IPF (n = 30) [52]. The drug was safe and well tolerated, with 100% of patients completing the 24-week treatment period. In addition, while patients in the lowest-dose cohort experienced a decline in FVC comparable to that observed in placebo arms of previous IPF trials [53], the highest-dose cohort showed a trend toward stabilization of FVC and decreased binding of C1q (a collagen-like component of the complement system) to anti-Col V antibodies consistent with an IW001-induced effect on anti-Col V antibody binding and activity.
Benefits of ketogenic diet in a pediatric patient with Ehlers-Danlos syndrome and STXBP1-related epileptic encephalopathy
Published in International Journal of Neuroscience, 2022
Aycan Ünalp, Hande Gazeteci Tekin, Pakize Karaoğlu, Zeynep Akışın
Our patient had the diagnosis of EDS when she was three years old. On physical examination she had hyperelastic skin and absent deep tendon reflexes. Type V collagen mutations in classical type EDS include heterozygous nonsense, frameshift or splice-site mutations of COL5A1. These mutations cause the inability to produce abnormal protein by the premature stop-codon of the mutant mRNA. As a result, alpha-1 chain production of type V collagen decreases [6]. Focal epilepsies are the most common seizure type seen in EDS. In EDS seizures were reported with brain malformations such as frontal gliosis, Dandy-Walker malformation, basilar artery hypoplasia, left hemispheric atrophy, venous parietal angioma, intracranial hemorrhage, and stroke [7]. The brain imaging of our patient showed mild atrophy with hyperintense signal changes on periventricular regions which can be attributed to her refractory seizures over a long period of time.
The first experience of denosumab therapy on patients with Ehlers–Danlos syndrome and osteoporosis: detailed observation of two patients
Published in Modern Rheumatology Case Reports, 2021
Sako Yasukawa, Masashi Uehara, Takako Suzuki, Masaki Nakano, Tomoki Kosho, Yukio Nakamura, Jun Takahashi
A 59-year-old man with classical EDS caused by a mutation in the gene for type V collagen and osteoporosis received a 48-month course of denosumab therapy. His laboratory data and BMD are presented in Table 1. At the age of 3 years, his mother noticed an abnormal curvature of his spinal column and was later diagnosed with EDS. The patient wore a corset for scoliosis until the age of 16 years and subsequently underwent follow-up examinations. He experienced back pain and numbness in the limbs from the age of 48 years. Due to deterioration of symptoms, the patient underwent a posterior spinal fusion at age 53 years (Figure 1(a,b)). There was no loss of lumbar BMD, but it may have been possible that the bone density could not be accurately assessed in the lumbar spine due to the posterior thoracolumbar fixation. Therefore, the treatment for osteoporosis was determined on the basis of the reduced hip BMD. Furthermore, we believed that the treatment of osteoporosis was necessary in order to make bone strength the predominant condition for which a posterior thoracolumbar fixation was performed. He began subcutaneous administration of parathyroid hormone (PTH); however, he discontinued its use after one and a half years due to adverse reactions that included an itching sensation throughout the body.
Related Knowledge Centers
- Collagen
- Dermoepidermal Junction
- Metalloproteinase
- Type I Collagen
- Extracellular Matrix
- Ehlers–Danlos Syndromes
- Collagen, Type V, Alpha 1
- Collagen, Type V, Alpha 2
- Collagen, Type V, Alpha 3