Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Echinoderms: Structure and Possible Functions

Abstract

Echinoderms are one of the most ancient groups of invertebrates. The study of their genomes has made it possible to conclude that these animals have a wide variety of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The phylogenetic analysis shows that the MMPs and TIMPs underwent repeated duplication and active divergence after the separation of Ambulacraria (Echinodermata+Hemichordata) from the Chordata. In this regard the homology of the proteinases and their inhibitors between these groups of animals cannot be established. However, the MMPs of echinoderms and vertebrates have a similar domain structure. Echinoderm proteinases can be structurally divided into three groups—archetypal MMPs, matrilysins, and furin-activatable MMPs. Gelatinases homologous to those of vertebrates were not found in genomes of studied species and are probably absent in echinoderms. The MMPs of echinoderms possess lytic activity toward collagen type I and gelatin and play an important role in the mechanisms of development, asexual reproduction and regeneration. Echinoderms have a large number of genes encoding TIMPs and TIMP-like proteins. TIMPs of these animals, with a few exceptions, have a structure typical for this class of proteins. They contain an NTR domain and 10–12 conservatively located cysteine residues. Repeated duplication and divergence of TIMP genes of echinoderms was probably associated with an increase in the functional importance of the proteins encoded by them in the physiology of the animals.

Possible Mechanisms of Stiffness Changes Induced by Stiffeners and Softeners in Catch Connective Tissue of Echinoderms

“…According to the authors, tensilins include a protein from Apostichopus japonicus (NCBI accession number PIK52999) [ 28 ] and one from the Cuvierian tubules of Holothuria forskali (NCBI accession number AQR59058), which we will mention below [ 29 ]. Later, the TIMPs of the echinoderms were classified into 5 groups [ 30 ]. The analysis showed that tensilins belong to group V of TIMPs.…”

“…It is possible that some TIMPs of echinoderms are neither stiffening proteins nor inhibitors of MMPs. Some TIMPs of echinoderms are assumed to have metalloproteinase-independent activities, as suggested in mammalian TIMPs [ 30 ].…”

“…Although the reaction speed of proteases is relatively slow, the partial involvement of proteases may occur in the softening of catch connective tissue. Echinoderms have many metalloprotease genes [ 23 , 27 , 30 ], and a metalloprotease was found in the body wall of the sea cucumber Apostichopus japonicus [ 38 ]. It is possible that a protease that causes degradation of the microfibrils is involved in the extreme softening of the body wall dermis of a sea cucumber Stichopus badionotus [ 39 ] (see the next section).…”

Proteases and HPV-Induced Carcinogenesis

“…Metalloproteases (MMPs) are critical enzymes which are responsible for the degradation of the extracellular matrix (ECM) [108]. These proteases participate in various physiological processes, especially in connective tissue remodeling, such as the postpartum involution of the uterus, ovulation, and wound healing, and in pathological processes such as joint destruction in rheumatoid diseases [109,110]. It is known that metalloproteases are secreted as zymogens, and that they are activated proteolytically.…”

A novel delivery vehicle for copper peptides

“…4 Due to the presence of matrix metalloproteinase tissue inhibitors (TIMPs) that inhibit its secretion, healthy skin contains extremely low levels of MMP-1, thereby retarding the breakdown of collagen (the main extracellular matrix backbone). [5][6][7] In addition, exposing skin to UV radiation produces reactive oxygen species (ROS) that damage the skin barrier and/or DNA. 8,9 Excessive accumulation of ROS leads to oxidative stress, which further accelerates premature skin aging.…”