Extracellular matrix components: An intricate network of possible biomarkers for lysosomal storage disorders?

Batzios, Spyros; Zafeiriou, Dimitrios I.; Papakonstantinou, Eleni

doi:10.1016/j.febslet.2013.02.035

Cited by 17 publications

(11 citation statements)

References 148 publications

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“…Apart from a single study in a skin biopsy of a patient with MBD, biochemical and morphologic studies on extracellular matrix or bone pathology have not been performed for MBD. Future studies similar to those performed for numerous other LSDs and for Morquio‐A disease may serve for a better understanding of the clinical differences between Morquio‐A disease and MBD (eg, why surgical operations in MBD patients differ significantly from those with Morquio‐A disease both in regards to the types of intervention, and in regards to the age at which these surgeries become necessary …”

Section: Discussionmentioning

confidence: 93%

Morquio‐B disease: Clinical and genetic characteristics of a distinct GLB1‐related dysostosis multiplex

et al. 2019

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Background Morquio‐B disease (MBD) is a distinct GLB1‐related dysostosis multiplex involving the trabecular parts of long bones and spine, presenting a mild phenocopy of GALNS‐related Morquio‐A disease. Methods We analyzed 63 (n = 62 published) cases with MBD to describe their clinical, biochemical and genetic features. Results Forty‐one of 51 cases with informative clinical data had pure MBD including progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly, odontoid hypoplasia. Ten of 51 had MBD plus neuronopathic manifestations including intellectual/developmental/speech delay, spasticity, ataxia dystonia. Corneal clouding, cardiac valve pathology, hepatosplenomegaly, spinal cord compression were infrequent and atlantooccipital dislocation, cardiomyopathy and cherry red spot were never reported. Urinary glycosaminoglycan and oligosaccharide excretion was consistently abnormal. Keratan sulphate‐derived oligosaccharides were only detected using LC‐MS/MS‐based methods. Residual β‐galactosidase activities measured against synthetic substrates were 0%‐17%. Among 28 GLB1 variants, W273 L (34/94 alleles) and T500A (11/94 alleles) occurred most frequently. W273L was invariably associated with pure MBD. Pure MBD also was reported in a case homozygous for R201H, and in the majority of cases carrying the T500A variant. Homozygous Y333C and G438E were associated with MBD plus neuronopathic manifestations. T82M, R201H, and H281Y, observed in seven alleles, previously have been found sensitive to experimental chaperones. Conclusion Data provide a basis for future systematic collection of clinical, biochemical, morphologic, and genetic data of this ultra‐rare condition.

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Section: Discussionmentioning

confidence: 93%

Morquio‐B disease: Clinical and genetic characteristics of a distinct GLB1‐related dysostosis multiplex

et al. 2019

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“…It is noteworthy that both regions in the LF-LCL group had enriched ECM and homeostasis GO terms. The ECM is composed of fibrous collagen and non-collagen proteins (glycoproteins and proteoglycans), which bind to proteins on cell surface promoting a variety of cellular responses including survival, proliferation, adhesion, and migration [ 49 , 50 ]. In the present study, both oviduct regions of the LF-LCL group showed enrichment of the ECM pathways.…”

Section: Resultsmentioning

confidence: 99%

Size of the Ovulatory Follicle Dictates Spatial Differences in the Oviductal Transcriptome in Cattle

et al. 2015

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In cattle, molecular control of oviduct receptivity to the embryo is poorly understood. Here, we used a bovine model for receptivity based on size of the pre-ovulatory follicle to compare oviductal global and candidate gene transcript abundance on day 4 of the estrous cycle. Growth of the pre-ovulatory follicle (POF) of Nelore (Bos indicus) cows was manipulated to produce two groups: large POF large corpus luteum (CL) group (LF-LCL; greater receptivity) and small POF-small CL group (SF-SCL). Oviductal samples were collected four days after GnRH-induced ovulation. Ampulla and isthmus transcriptome was obtained by RNA-seq, regional gene expression was assessed by qPCR, and PGR and ERa protein distribution was evaluated by immunohistochemistry. There was a greater abundance of PGR and ERa in the oviduct of LF-LCL animals thus indicating a greater availability of receptors and possibly sex steroids stimulated signaling in both regions. Transcriptomic profiles indicated a series of genes associated with functional characteristics of the oviduct that are regulated by the periovulatory sex steroid milieu and that potentially affect oviductal receptivity and early embryo development. They include tissue morphology changes (extra cellular matrix remodeling), cellular changes (proliferation), and secretion changes (growth factors, ions and metal transporters), and were enriched for the genes with increased expression in the LF-LCL group. In conclusion, differences in the periovulatory sex steroid milieu lead to different oviductal gene expression profiles that could modify the oviductal environment to affect embryo survival and development.

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“…In MPSs, the lysosomal accumulation of undigested GAGs is considered the "primum movens" of the subsequent functional cell impairment; however, evidence demonstrates that the accumulation of storage material does not occur only in the lysosomes, but also on the cell surface and ECM where GAGs form proteoglycans through their covalent binding to a core protein [105,106,109]. The accumulation of storage material in non-lysosomal compartments accounts for impaired cell signaling and trafficking, protein unfolding, abnormal autophagy, alterations of intracellular calcium homeostasis, lysolipid accumulation, and modifications in other cellular processes that ultimately lead to the MPS phenotypes [150][151][152][153][154][155][156][157][158][159].…”

Section: Cathepsin Involvement In the Pathophysiology Of Mucopolysaccmentioning

confidence: 99%

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

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Extracellular matrix components: An intricate network of possible biomarkers for lysosomal storage disorders?

Cited by 17 publications

References 148 publications

Morquio‐B disease: Clinical and genetic characteristics of a distinct GLB1‐related dysostosis multiplex

Morquio‐B disease: Clinical and genetic characteristics of a distinct GLB1‐related dysostosis multiplex

Size of the Ovulatory Follicle Dictates Spatial Differences in the Oviductal Transcriptome in Cattle

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

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