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      Expression Profiling of ADAMTS (L) Superfamily of Genes in Various Human Eye Tissues

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          Abstract

          Background:

          A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a superfamily of extracellular proteinases found in both mammals and invertebrates. Although there is some evidence about the role of ADAMTSs in ocular diseases such as glaucoma and ectopia lentis, but there is little information about the expression patterns of ADAMTS-1–20 and ADAMTS-like ( ADAMTSL-1–6 and PAPLN) genes in human ocular tissues. This study aimed to evaluate the expression profiling of ADAMTS(L) superfamily of genes in different ocular tissues based on age.

          Methods:

          In 2019, nine human donated eye globes were provided from the Central Eye Bank of Iran, and were divided into three different groups based on age (under 3 yr old, between 20 to 50 and upper 50 yr old). To assess expression patterns of ADAMTS(L) genes in different ocular tissues including trabecular meshwork, lens, retinal pigment epithelium, macula, and optic nerve in the three age groups, total RNA was extracted from the tissues and reverse transcription polymerase chain reaction followed by Real-time PCR was performed.

          Results:

          We demonstrated not only each member of ADAMTS(L) superfamily shows different expression pattern between the five investigated ocular tissues, but also some members have differential expressions among the investigated age groups in same tissues.

          Conclusion:

          Differential expression of ADAMTS(L) genes in ocular tissues from different age groups could explain some functional aspects of the tissues and also may be used as prognostic and diagnostic biomarkers for ocular diseases and pathologies. Further studies are required to explore their functional roles associated with ocular pathologies.

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          Most cited references35

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          The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

          The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future.
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            ADAMTS proteins in human disorders

            ADAMTS proteins are a superfamily of 26 secreted molecules comprising two related, but distinct families. ADAMTS proteases are zinc metalloendopeptidases, most of whose substrates are extracellular matrix (ECM) components, whereas ADAMTS-like proteins lack a metalloprotease domain, reside in the ECM and have regulatory roles vis-à-vis ECM assembly and/or ADAMTS activity. Evolutionary conservation and expansion of ADAMTS proteins in mammals is suggestive of crucial embryologic or physiological roles in humans. Indeed, Mendelian disorders or birth defects resulting from naturally occurring ADAMTS2, ADAMTS3, ADAMTS10, ADAMTS13, ADAMTS17, ADAMTS20, ADAMTSL2 and ADAMTSL4 mutations as well as numerous phenotypes identified in genetically engineered mice have revealed ADAMTS participation in major biological pathways. Important roles have been identified in a few acquired conditions. ADAMTS5 is unequivocally implicated in pathogenesis of osteoarthritis via degradation of aggrecan, a major structural proteoglycan in cartilage. ADAMTS7 is strongly associated with coronary artery disease and promotes atherosclerosis. Autoantibodies to ADAMTS13 lead to a platelet coagulopathy, thrombotic thrombocytopenic purpura, which is similar to that resulting from ADAMTS13 mutations. ADAMTS proteins have numerous potential connections to other human disorders that were identified by genome-wide association studies. Here, we review inherited and acquired human disorders in which ADAMTS proteins participate, and discuss progress and prospects in therapeutics.
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              Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations.

              Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. Mutations cause ECM dysfunction by combinations of two mechanisms. First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. Second, secretion of mutant protein can disturb crucial ECM interactions, structure and stability. Moreover, recent experiments suggest that endoplasmic reticulum (ER) stress, caused by mutant misfolded ECM proteins, contributes to the molecular pathology. Targeting ER stress might offer a new therapeutic strategy.
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                Author and article information

                Journal
                Iran J Public Health
                Iran J Public Health
                IJPH
                Iranian Journal of Public Health
                Tehran University of Medical Sciences
                2251-6085
                2251-6093
                December 2023
                : 52
                : 12
                : 2630-2642
                Affiliations
                [1. ]Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [2. ]School of Biology, Damghan University, Damghan, Iran
                [3. ]Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                Author notes
                Article
                IJPH-52-2630
                10.18502/ijph.v52i12.14324
                10903312
                9ea4fe25-46af-441c-a560-b2786109dd5e
                Copyright© 2023 Suri et al. Published by Tehran University of Medical Sciences.

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International license. ( https://creativecommons.org/licenses/by-nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited

                History
                : 20 July 2022
                : 14 October 2022
                Categories
                Original Article

                Public health
                adamts proteins,gene expression,eye
                Public health
                adamts proteins, gene expression, eye

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