A novel hydra matrix metalloproteinase (HMMP) functions in extracellular matrix degradation, morphogenesis and the maintenance of differentiated cells in the foot process

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 907-920 ◽  
Author(s):  
A.A. Leontovich ◽  
J. Zhang ◽  
K. Shimokawa ◽  
H. Nagase ◽  
M.P. Sarras
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Longitudinal Axis ◽  
The Body ◽  
Mmp Inhibitors ◽  
Functional Studies ◽  
Cell Transdifferentiation ◽  
Basal Disk ◽  
Foot Process ◽  
Hemopexin Domain

As a member of Cnidaria, the body wall of hydra is structurally reduced to an epithelial bilayer with an intervening extracellular matrix (ECM). Biochemical and cloning studies have shown that the molecular composition of hydra ECM is similar to that seen in vertebrates and functional studies have demonstrated that cell-ECM interactions are important to developmental processes in hydra. Because vertebrate matrix metalloproteinases (MMPs) have been shown to have an important role in cell-ECM interactions, the current study was designed to determine whether hydra has homologues of these proteinases and, if so, what function these enzymes have in morphogenesis and cell differentiation in this simple metazoan. Utilizing a PCR approach, a single hydra matrix metalloproteinase, named HMMP was identified and cloned. The structure of HMMP was similar to that of vertebrate MMPs with an overall identity of about 35%. Detailed structural analysis indicated some unique features in (1) the cysteine-switch region of the prodomain, (2) the hinge region preceding the hemopexin domain, and (3) the hemopexin domain. Using a bacterial system, HMMP protein was expressed and folded to obtain an active enzyme. Substrate analysis studies indicated that recombinant HMMP could digest a number of hydra ECM components such as hydra laminin. Using a fluorogenic MMP substrate assay, it was determined that HMMP was inhibited by peptidyl hydroxamate MMP inhibitors, GM6001 and matlistatin, and by human recombinant TIMP-1. Whole-mount in situ studies indicated that HMMP mRNA was expressed in the endoderm along the entire longitudinal axis of hydra, but at relatively high levels at regions where cell-transdifferentiation occurred (apical and basal poles). Functional studies using GM6001 and TIMP-1 indicated that these MMP inhibitors could reversibly block foot regeneration. Blockage of foot regeneration was also observed using antisense thio-oligo nucleotides to HMMP introduced into the endoderm of the basal pole using a localized electroporation technique. Studies with adult intact hydra found that GM6001 could also cause the reversible de-differentiation or inhibition of transdifferentiation of basal disk cells of the foot process. Basal disk cells are adjacent to those endoderm cells of the foot process that express high levels of HMMP mRNA. In summary, these studies indicate that hydra has at least one MMP that is functionally tied to morphogenesis and cell transdifferentiation in this simple metazoan.

A 25.7 × 10(3) M(r) hydra metalloproteinase (HMP1), a member of the astacin family, localizes to the extracellular matrix of Hydra vulgaris in a head-specific manner and has a developmental function

Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1591-1602 ◽  
Author(s):  
L. Yan ◽  
G.H. Pollock ◽  
H. Nagase ◽  
M.P. Sarras
Keyword(s):  
Extracellular Matrix ◽  
Gelatin Zymography ◽  
Longitudinal Axis ◽  
The Body ◽  
Cdna Clones ◽  
Head Region ◽  
Differential Distribution ◽  
Functional Studies ◽  
Type Iv ◽  
Sds Page

Hydra extracellular matrix (ECM) is composed of a number of components seen in vertebrate ECM such as laminin, type IV collagen, fibronectin, and heparan sulfate proteoglycan. A number of functional studies have shown that hydra ECM plays an important role in pattern formation and morphogenesis of this simple metazoan. The present study was designed to identify matrix degrading proteinases in hydra and determine their potential function in hydra morphogenesis. Using SDS-PAGE gelatin-zymography, five gelatinolytic bands were identified with relative molecular masses of 67 × 10(3), 51–58 × 10(3) (a triplet) and 25–29 × 10(3), respectively. Inhibition studies indicated that all of these gelatinases were metalloproteinases. Gelatin-zymography indicated that there was a differential distribution of these gelatinases along the longitudinal axis of hydra, with the 67 × 10(3) M(r) gelatinase being concentrated in the body column, while the 51–58 × 10(3) M(r) gelatinase triplet and the 25–29 × 10(3) M(r) gelatinase concentrated in the head region. Purification procedures were successfully developed for the 25–29 × 10(3) M(r) metalloproteinase which has been termed hydra metalloproteinase 1 (HMP1) and which appeared as a single band with a SDS-PAGE mobility of 25.7 × 10(3) M(r). The N-terminal sequence of purified HMP1 indicated that it has structural homology with metalloproteinases that belong to the astacin family. Subsequent cloning and sequencing of cDNA clones confirmed the identification of HMP1 as an astacin-like metalloproteinase. Immunocytochemical studies with antibodies generated against the purified enzyme and to a synthetic peptide indicated that HMP1 was localized to the ECM of tentacles. Functional studies were performed in which purified HMP1, anti-HMP1 IgG, or suspected substrates of HMP1 (e.g. growth factors such as TGF-beta 1) were introduced into the interepithelial compartment of hydra using a ‘DMSO loading’ procedure. These studies indicated that HMP1 has a functional role during a number of developmental processes such as head regeneration and cell differentiation/transdifferentiation of tentacle battery cells.

scholarly journals Matrix Metalloproteinase and Their Inhibitors Concentration and Activity Variations in Aqueous Humor and Plasma of Glaucoma Patients

2017 ◽  
Vol 68 (8) ◽  
pp. 1829-1833
Author(s):  
Iulia Maria Ciotu ◽  
Alina Constantin ◽  
Liliana Voinea ◽  
Valeriu Atanasiu
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Aqueous Humor ◽  
Open Angle Glaucoma ◽  
The Body ◽  
Plasma Samples ◽  
Open Angle ◽  
Aqueous Humor Outflow ◽  
Cataract Patients

Matrix metalloproteinases (MMPs) are a group of endopeptidases with the role of reorganizing the extracellular matrix of cells through the body. In aqueous humor MMPs have an important role in turnover regulation by acting on the constant remodeling of the trabecular mesh keeping at a constant level the trabecular resistance for a good aqueous humor outflow and consequently of the intraocular pressure.In this paper, we aimed to assess the levels of MMP-2/TIMP-1 and MMP-9/TIMP-2 ratio in aqueous humor samples and in the plasma of patients with open angle glaucoma and cataract patients that serves as control, and to evaluate the gelatinolytic activity MMP-2 and MMP-9 in aqueous humor samples. Aqueous humor and plasma samples were collected from 30 patients, 14 from open angle glaucoma and 16 from cataract patients. Levels of MMP-2, -9 and TIMP -1 and -2 were determined by zymography and immunoassays, using specific kits. The data obtained suggest the presence of a direct correlation between the levels and activity of MMP influencing the accumulation of abnormal matrix and may have an impact on the pathogenesis of open angle glaucoma.\

scholarly journals Matrix Metalloproteinase Inhibition in a Murine Model of Cavitary Tuberculosis Paradoxically Worsens Pathology

2018 ◽  
Vol 219 (4) ◽  
pp. 633-636 ◽  
Author(s):  
Alvaro A Ordonez ◽  
Supriya Pokkali ◽  
Julian Sanchez-Bautista ◽  
Mariah H Klunk ◽  
Michael E Urbanowski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mycobacterium Tuberculosis ◽  
Matrix Metalloproteinases ◽  
Pulmonary Tuberculosis ◽  
Matrix Metalloproteinase ◽  
Murine Model ◽  
Potent Inhibitor ◽  
Mmp Inhibitors

Abstract Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in tuberculosis pathogenesis and cavitation. In particular, MMP-7 is induced by hypoxia and highly expressed around pulmonary cavities of Mycobacterium tuberculosis–infected C3HeB/FeJ mice. In this study, we evaluated whether administration of cipemastat, an orally available potent inhibitor of MMP-7, could reduce pulmonary cavitation in M. tuberculosis–infected C3HeB/FeJ mice. We demonstrate that, compared with untreated controls, cipemastat treatment paradoxically increases the frequency of cavitation (32% vs 7%; P = .029), immunopathology, and mortality. Further studies are needed to understand the role of MMP inhibitors as adjunctive treatments for pulmonary tuberculosis.

scholarly journals MATRIX METALLOPROTEINASES 2 AND 9 IN AVOCATION OF MULTITUDINAL COMPLICATIONS IN EXPLICITLY TO CARCINOMA: REVIEW

2016 ◽  
Vol 10 (1) ◽  
pp. 47
Author(s):  
Stellaa Robertson ◽  
Asha K Rajan ◽  
Maheshwaran A ◽  
Senthilnathan B ◽  
Sagali Phani Venkata Satya Sai Anuroopa
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Inflammatory Cells ◽  
The Body ◽  
Matrix Metalloproteinase 2 ◽  
Antiangiogenic Agents ◽  
Surface Receptors ◽  
Calcium Dependent ◽  
Enormous Number

ABSTRACTMatrix metalloproteinases (MMPs) are a large group of calcium-dependent zinc containing endopeptidases which are mainly concerned with theremodeling of tissue along with degradation of the extracellular matrix. At the present scenario, there is knowledge of about 26 MMPs which are foundto be highly regulated by the growth hormones, cytokines, etc., present within the body. At times of normal homeostasis, their levels within the bodyare low, and their number usually increases at times of pathological conditions. Its generation is known to occur from the pro-inflammatory cells andconnective tissues. They may even lead to the process of apoptosis by its interactions with surface receptors. In the clinical trials sectors, various MMPsalong with their inhibitors are examined to import the properties of being a high biomarker in the cancer diagnosis, antiangiogenic agents, variousother disorders such as chronic allograft nephropathy, diabetic nephropathy, cardiovascular diseases, neuropathic pain, wound healing, angiogenesisprocesses, immune response, corneal ulceration, embryonic development, and nervous system disorders. As a result, enormous number of studies onthis particular enzyme in the marking of cancer and their elevation in the above-mentioned diseases has to be carried out so that it would remain asa useful tool in their diagnosis. The present work is designed to emphasize the concise review of MMPs, in particularly MMP-2 and MMP-9 along withtheir variant roles, keeping in mind, that it would be advantageous for the researchers to bring out more promising results and to intensify diagnosisof various infirmities, especially in cancer.Keywords: Matrix metalloproteinase-2, Matrix metalloproteinase-9, Biomarker, Matrix metalloproteinases, Carcinoma, Extracellular matrix,Malignancy, Gelatinases, Tumor.

Functional analysis of chondroitin 4 sulfate constituting osseointegration

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 18-20
Author(s):  
Shuhei Tsuchiya
Keyword(s):  
Functional Analysis ◽  
Extracellular Matrix ◽  
Dental Implants ◽  
Maxillofacial Surgery ◽  
The Body ◽  
Oral And Maxillofacial Surgery ◽  
Direct Connection ◽  
Tooth Replacement ◽  
Living Bone ◽  
Natural Tooth

Osseointegration can be defined as a direct connection, both structural and functional, between living bone and the surface of an artificial implant. Indeed, the word comes from the Greek term for 'bone' and 'to make whole'. In dentistry, once dental implants are placed, the body will react with osseointegration, enabling the implants to become a permanent part of the jaw. There are many benefits to this type of implant, compared with traditional tooth replacement options, not least that dental implants mimic the strength and functionality of a natural tooth. Dr Shuhei Tsuchiya is a researcher based in the Division of Oral and Maxillofacial Surgery at Nagoya University, Japan, who is interested in a range of areas, including regenerative medicine and the extracellular matrix. One of his key preoccupations, though, is shedding light on osseointegration. He and his team are working to unravel the mysteries of the mechanism.

scholarly journals Quantitative Evaluation of Osteocyte Morphology and Bone Anisotropic Extracellular Matrix in Rat Femur

2021 ◽  
Author(s):  
Takuya Ishimoto ◽  
Keita Kawahara ◽  
Aira Matsugaki ◽  
Hiroshi Kamioka ◽  
Takayoshi Nakano
Keyword(s):  
Extracellular Matrix ◽  
Longitudinal Axis ◽  
Rat Femur ◽  
Male Rat ◽  
Mechanical Stimuli ◽  
Axis Orientation ◽  
Principal Stress Direction ◽  
Mechanical Integrity ◽  
Osteocyte Lacunae ◽  
The Relationship

AbstractOsteocytes are believed to play a crucial role in mechanosensation and mechanotransduction which are important for maintenance of mechanical integrity of bone. Recent investigations have revealed that the preferential orientation of bone extracellular matrix (ECM) mainly composed of collagen fibers and apatite crystallites is one of the important determinants of bone mechanical integrity. However, the relationship between osteocytes and ECM orientation remains unclear. In this study, the association between ECM orientation and anisotropy in the osteocyte lacuno-canalicular system, which is thought to be optimized along with the mechanical stimuli, was investigated using male rat femur. The degree of ECM orientation along the femur longitudinal axis was significantly and positively correlated with the anisotropic features of the osteocyte lacunae and canaliculi. At the femur middiaphysis, there are the osteocytes with lacunae that highly aligned along the bone long axis (principal stress direction) and canaliculi that preferentially extended perpendicular to the bone long axis, and the highest degree of apatite c-axis orientation along the bone long axis was shown. Based on these data, we propose a model in which osteocytes can change their lacuno-canalicular architecture depending on the mechanical environment so that they can become more susceptible to mechanical stimuli via fluid flow in the canalicular channel.

scholarly journals Optical Microscopy and the Extracellular Matrix Structure: A Review

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1760
Author(s):  
Joshua J. A. Poole ◽  
Leila B. Mostaço-Guidolin
Keyword(s):  
Extracellular Matrix ◽  
Confocal Microscopy ◽  
Laser Scanning ◽  
Biological Tissues ◽  
The Body ◽  
Stimulated Emission ◽  
Substantial Part ◽  
Fluorescence Lifetime Imaging ◽  
Structured Illumination ◽  
Structured Illumination Microscopy

Biological tissues are not uniquely composed of cells. A substantial part of their volume is extracellular space, which is primarily filled by an intricate network of macromolecules constituting the extracellular matrix (ECM). The ECM serves as the scaffolding for tissues and organs throughout the body, playing an essential role in their structural and functional integrity. Understanding the intimate interaction between the cells and their structural microenvironment is central to our understanding of the factors driving the formation of normal versus remodelled tissue, including the processes involved in chronic fibrotic diseases. The visualization of the ECM is a key factor to track such changes successfully. This review is focused on presenting several optical imaging microscopy modalities used to characterize different ECM components. In this review, we describe and provide examples of applications of a vast gamut of microscopy techniques, such as widefield fluorescence, total internal reflection fluorescence, laser scanning confocal microscopy, multipoint/slit confocal microscopy, two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG, THG), coherent anti-Stokes Raman scattering (CARS), fluorescence lifetime imaging microscopy (FLIM), structured illumination microscopy (SIM), stimulated emission depletion microscopy (STED), ground-state depletion microscopy (GSD), and photoactivated localization microscopy (PALM/fPALM), as well as their main advantages, limitations.

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