The role of matrix metalloproteinases in aging: Tissue remodeling and beyond

Freitas‐Rodríguez, Sandra; Folgueras, Alicia R.; López-Otı́n, Carlos

doi:10.1016/j.bbamcr.2017.05.007

Cited by 214 publications

(187 citation statements)

References 98 publications

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“…10 Furthermore, activated MAPKs (ERK1/2, p38, JNK) and PI3K/Akt pathways could promote the type I procollagen expression in human dermal fibroblasts. For example, ECM-receptor interaction is an important pathway among them.…”

Section: Discussionmentioning

confidence: 99%

miRNA expression profiling uncovers a role of miR‐302b‐3p in regulating skin fibroblasts senescence

Tan

Yang

et al. 2019

J of Cellular Biochemistry

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Numbers of emerging evidence suggest that variable microRNA (miRNA) expression facilitates the aging process. In this study, we distinguished aberrant miRNA expression in aged skin and explored the biological functions and potential mechanism of upregulated miR‐302b‐3p. At first, miRNA microarray analysis was examined to explore miRNA expression profiling in the skin of aging mice model by D‐galactose (d‐gal) injection. We identified 29 aberrant miRNAs in aged mice skin. Next, KEGG enrichment analysis was conducted with DIANA‐miPath v3.0, which was revealed that enrichment pathways involved in such processes as extracellular matrix‐receptor interaction, MAPK signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway. The target genes of deregulated miRNAs were predicted from four bioinformatic algorithms (miRDB, Targetscan, miRwalk, and Tarbase). The interaction network of miRNAs and their targets were visualized using Cytoscape software. As a result, we found that some hub genes (including JNK2, AKT1/2/3, PAK7, TRPS1, BCL2L11, and IKZF2) were targeted by 12 potential miRNAs (including miR‐302b‐3p, miR‐291a‐5p, miR‐139‐3p, miR‐467c‐3p, miR‐186‐3p, etc.). Subsequently, we identified five upregulated miRNA via quantitative polymerase chain reaction and all of them were confirmed increased significantly in aged skin tissues compared with young control tissues. Among them, high expression of miR‐302b‐3p was verified in both aged skin tissues and senescence fibroblasts. Furthermore, miR‐302b‐3p mimic accelerated skin fibroblast senescence and suppressed the longevity‐associated gene Sirtuin 1(Sirt1) expression, whereas miR‐302b‐3p inhibitor could delay skin fibroblast senescence and contribute Sirt1 expression. In addition, we demonstrated that c‐Jun N‐terminal kinase 2(JNK2) is a direct target of miR‐302b‐3p by a luciferase reporter assay. An inverse correlation was verified in fibroblasts between miR‐302b‐3p and JNK2. Most importantly, siRNA JNK2 confirmed that low expression of JNK2 could accelerate fibroblasts senescence. In conclusion, our results indicated that overexpressed miR‐302b‐3p plays an important biological role in accelerating skin aging process via directly targeting JNK2 gene.

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Section: Discussionmentioning

confidence: 99%

miRNA expression profiling uncovers a role of miR‐302b‐3p in regulating skin fibroblasts senescence

Tan

Yang

et al. 2019

J of Cellular Biochemistry

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“…Bu enzimler kataliz mekanizması temelinde; aspartik, metallo, sistein, serin ve treonin proteazları olarak sınıflandırılmaktadır. 31 MMP'ler hücrelerden salınarak plazma membranına bağlanan, matriksin yıkımına neden olan, Zn ++ ve Ca ++ 'a bağımlı bir nötral endopeptidaz ailesidir. [32][33][34][35] MMP enzim ailesi; embriyonik gelişim, organ morfogenezi, ovulasyon, embriyo implantasyonu, yara iyileşmesi, anjiyogenez ve apoptozda kilit rol oynamaktadır.…”

Section: Matri̇ks Metalloprotei̇nazlarunclassified

Skin Aging and Effects of Matrix Metalloproteinase Enzymes on Aging

Uzun¹,

Demirezer²

2019

J Lit Pharm Sci

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206 ilt yaşlanması, günümüzde hem erkek hem de kadınları etkileyen önemli bir sorun olarak görülmektedir. Son dönem araştırmalarında, yaşlanma artık sadece hücreye özgü olan ve esas olarak genomik dengesizlik, telomer kısalması, epigenetik değişiklikler ve proteostazinin neden Cilt Yaşlanması ve Matriks Metalloproteinaz Enzimlerinin Yaşlanma Üzerine Etkileri Ö ÖZ ZE ET T Cilt yaşlanması hem kadın hem de erkekler için modern zamanların önemli sorunları arasında yer almaktadır. Yaşlanma yapısal ve moleküler bozulma ile beraber, derinin fonksiyon ve görüntüsünü etkileyen yavaş ve progresif seyreden karmaşık bir süreçtir. Bu süreç çeşitli iç ve dış etkenler ile şekillenmektedir. Temel olarak cilt yaşlanması; zamana bağlı olarak gelişen kronolojik yaşlanma (intrensek yaşlanma) ve başta güneşin zararlı ışınlarına maruziyet olmak üzere; sigara ve aşırı alkol kullanımı, yetersiz beslenme gibi olumsuz çevresel faktörlere bağlı olarak gelişen ekstrensek yaşlanma olmak üzere iki farklı şekilde gerçekleşmektedir. Deride görülen değişikliklerin %90'ından fazlası kronik güneş hasarının yol açtığı çevresel etkilere bağlıdır. Bu nedenle ekstrensek yaşlanma, aynı zamanda fotoyaşlanma olarak anılmaktadır. Yaşlanmanın önemli nedenlerinden olan matriks metalloproteinaz (MMP)lar ise ekstraselüler matriksteki kollajen ve diğer proteinlerin parçalanmasından sorumlu ana enzim grubudur. Kollajen, bağ dokusunun temel yapısal bileşenidir ve bozulması yaşlı görünmenin temel nedenlerindendir. MMP ailesi kolajenazlar, jelatinazlar, stromelisinler, matrilisinler, membran tipi MMP'ler ve diğer sınıflandırılmamış MMP'ler olmak üzere altı gruba ayrılmaktadır. MMP'ler yaşlanma ile ilgili olmalarının yanı sıra, birçok kanser çeşidinin oluşması ve ilerlemesiyle de yakından ilişkilidir. Bu çalışmada, cilt yaşlanmasına neden olan etmenler, organizmada meydana gelen birçok hastalıkla ilişkili önemli bir enzim ailesi olan MMP enzimleri ve yaşlanma ile olan ilişkileri araştırılmıştır.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Matriks metalloproteinazlar; deri yaşlanması; kollajenazlar A AB BS S T TR RA AC CT T Skin aging is one of the major problems of modern times for both men and women. Aging is a complicated and slow progressive process that affects the function and appearance of the skin with structural and molecular deterioration. This process is shaped by various internal and external factors. Skin aging as a basis takes place in two different ways: time-dependent chronological aging (intrinsic aging) and extrinsic aging due to negative environmental factors such as smoking and excessive alcohol use, and malnutrition. More than 90% of the skin changes are due to the environmental effects caused by chronic sun damage. Therefore, extrinsic aging is also referred to as photoaging. Matrix metalloproteinases (MMPs), a major cause of aging, are the main enzyme group responsible for the breakdown of collagen and other proteins in the extracellular matrix. Collagen is the main structural component of connective tissue, and its degradation is ...

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“…MMP activity is regulated by endogenous, tight-binding tissue inhibitors of metalloproteinases (TIMPs). Abnormal MMP expression and activity have been observed in cancer, cardiac remodeling and aneurysm formation, impaired wound healing, neurodegeneration, and after UV radiation exposure of the aging skin and the cornea [40]. The family of endogenous tissue-inhibitors of metalloproteinases (TIMPs) consists of 4 proteins that target protease activity of MMPs, ADAMs and ADAM-TSs.…”

Section: Regulation Of Physiological Processesmentioning

confidence: 99%

Proteases: Pivot Points in Functional Proteomics

Verhamme

Leonard

Perkins

2018

Functional Proteomics

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Proteases drive the life cycle of all proteins, ensuring the transportation and activation of newly minted, would-be proteins into their functional form while recycling spent or unneeded proteins. Far from their image as engines of protein digestion, proteases play fundamental roles in basic physiology and regulation at multiple levels of systems biology. Proteases are intimately associated with disease and modulation of proteolytic activity is the presumed target for successful therapeutics. “Proteases: Pivot Points in Functional Proteomics” examines the crucial roles of proteolysis across a wide range of physiological processes and diseases. The existing and potential impacts of proteolysis-related activity on drug and biomarker development are presented in detail. All told the decisive roles of proteases in four major categories comprising 23 separate sub-categories are addressed. Within this construct, 15 sets of subject-specific, tabulated data are presented that include identification of proteases, protease inhibitors, substrates and their actions. Said data are derived from and confirmed by over 300 references. Cross comparison of datasets indicates that proteases, their inhibitors/promoters and substrates intersect over a range of physiological processes and diseases, both chronic and pathogenic. Indeed, “Proteases: Pivot Points …” closes by dramatizing this very point through association of (pro)Thrombin and Fibrin(ogen) with: hemostasis, innate immunity, cardiovascular and metabolic disease, cancer, neurodegeneration and bacterial self-defense.

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The role of matrix metalloproteinases in aging: Tissue remodeling and beyond

Cited by 214 publications

References 98 publications

miRNA expression profiling uncovers a role of miR‐302b‐3p in regulating skin fibroblasts senescence

miRNA expression profiling uncovers a role of miR‐302b‐3p in regulating skin fibroblasts senescence

Skin Aging and Effects of Matrix Metalloproteinase Enzymes on Aging

Proteases: Pivot Points in Functional Proteomics

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