The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease DOI Open Access
Marta Wołosowicz, Sławomir Prokopiuk, Tomasz W. Kamiński

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13691 - 13691

Published: Dec. 21, 2024

Matrix metalloproteinase-2 (MMP-2), a zinc-dependent enzyme, plays critical role in the degradation and remodeling of extracellular matrix (ECM). As member gelatinase subgroup metalloproteinases, MMP-2 is involved variety physiological processes, including tissue repair, wound healing, angiogenesis, embryogenesis. It primarily responsible for type IV V collagen, fibronectin, laminin, elastin, which are essential components ECM. secreted as an inactive pro-enzyme (proMMP-2) activated through proteolytic cleavage, with its activity being precisely regulated by inhibitors metalloproteinases (TIMPs). Dysregulation has been linked to pathological conditions, cardiovascular diseases, diabetic complications, kidney cancer. In it contributes vascular remodeling, atherosclerosis, aneurysms, while fibrotic mediates excessive ECM leading scarring. diabetes, elevated exacerbates complications such nephropathy, retinopathy, disease. cancer, facilitates tumor invasion metastasis degrading promoting angiogenesis. Despite roles both targeting therapeutic purposes presents challenges due dual functions raising concerns about unplanned consequences impaired healing or damage. These underscore need future research focus on developing selective modulators that can balance their under specific disease environments. Clinical trials modulation highlight potential inhibitors, those MMP-2, reduce progression fibrosarcoma, breast, lung cancers. This paper reviews structure, function, regulation involvement pathogenesis, implications modulating activity.

Language: Английский

Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation DOI Open Access
Samar A. Antar,

Nada A. Ashour,

Mohamed E. Marawan

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 4004 - 4004

Published: Feb. 16, 2023

Most chronic inflammatory illnesses include fibrosis as a pathogenic characteristic. Extracellular matrix (ECM) components build up in excess to cause or scarring. The fibrotic process finally results organ malfunction and death if it is severely progressive. Fibrosis affects nearly all tissues of the body. associated with inflammation, metabolic homeostasis, transforming growth factor-β1 (TGF-β1) signaling, where balance between oxidant antioxidant systems appears be key modulator managing these processes. Virtually every system, including lungs, heart, kidney, liver, can affected by fibrosis, which characterized an excessive accumulation connective tissue components. Organ frequently caused remodeling, also linked high morbidity mortality. Up 45% fatalities industrialized world are damage any organ. Long believed persistently progressing irreversible, has now been revealed very dynamic preclinical models clinical studies variety systems. pathways from and/or main topics this review. Furthermore, different organs their effects was discussed. Finally, we highlight many principal mechanisms fibrosis. These could considered promising targets for development potential therapies important human diseases.

Language: Английский

Citations

136
TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis DOI Creative Commons
Lili Ren, Hua Miao, Yanni Wang

et al.

Aging and Disease, Journal Year: 2023, Volume and Issue: 14(5), P. 1633 - 1633

Published: Jan. 1, 2023

Fibrosis is the abnormal accumulation of extracellular matrix proteins such as collagen and fibronectin. Aging, injury, infections, inflammation can cause different types tissue fibrosis. Numerous clinical investigations have shown a correlation between degree liver pulmonary fibrosis in patients telomere length mitochondrial DNA content, both which are signs aging. Aging involves gradual loss function over time, results homeostasis and, ultimately, an organism's fitness. A major feature aging senescent cells. Senescent cells abnormally continuously accumulate late stages life, contributing to age-related deterioration, among other characteristics. Furthermore, generates chronic inflammation, decreases organ function. This finding suggests that closely related. The transforming growth factor-beta (TGF-β) superfamily plays crucial role physiological pathological processes aging, immune regulation, atherosclerosis, In this review, functions TGF-β normal organs, fibrotic tissues discussed: signalling altered with age indicator pathology associated addition, review discusses potential targeting noncoding.

Language: Английский

Citations

45
Epithelial–mesenchymal plasticity in kidney fibrosis DOI

Sudarat Hadpech,

Visith Thongboonkerd

genesis, Journal Year: 2023, Volume and Issue: 62(1)

Published: June 22, 2023

Summary Epithelial–mesenchymal transition (EMT) is an important biological process contributing to kidney fibrosis and chronic disease. This characterized by decreased epithelial phenotypes/markers increased mesenchymal phenotypes/markers. Tubular cells (TECs) are commonly susceptible EMT various stimuli, for example, transforming growth factor‐β (TGF‐β), cellular communication network factor 2, angiotensin‐II, fibroblast factor‐2, oncostatin M, matrix metalloproteinase‐2, tissue plasminogen activator (t‐PA), plasmin, interleukin‐1β, reactive oxygen species. Similarly, glomerular podocytes can undergo via these stimuli high glucose condition in diabetic of TECs leads tubulointerstitial glomerulosclerosis, respectively. Signaling pathways involved EMT‐mediated diverse complex. TGF‐β1/Smad Wnt/β‐catenin the major venues triggering podocytes. These two thus serve as therapeutic targets against fibrosis. To date, a number inhibitors have been identified characterized. As expected, majority affect pathways. In addition fibrosis, EMT‐targeted antifibrotic expected be effective treatment other organs/tissues.

Language: Английский

Citations

31
The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis DOI Creative Commons
Na Ren, Wenfeng Wang, Liang Zou

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 16, 2024

Renal fibrosis is increasingly recognized as a global public health problem. Acute kidney injury (AKI) and chronic disease (CKD) both result in renal fibrosis. Oxidative stress inflammation play central roles progressive are closely linked form vicious cycle which oxidative induces through various molecular mechanisms. Ample evidence has indicated that hyperactive nuclear factor kappa B (NF-ƙB) signaling pathway plays pivotal role Hyperactive NF-ƙB causes the activation recruitment of immune cells. Inflammation, turn, triggers production reactive oxygen species nitrogen by activating leukocytes resident These events mediate organ apoptosis, necrosis, Therefore, developing strategy to target important for effective treatment This Review summarizes effect on context AKI CKD (immunoglobulin A nephropathy, membranous diabetic hypertensive transplantation). Therapies targeting pathway, including natural products, also discussed. In addition, NF-ƙB-dependent non-coding RNAs involved crucial targets development treatments disease. provides clear pathophysiological rationale specific concept-driven therapeutic pathway.

Language: Английский

Citations

12
Exploring the Key Signaling Pathways and ncRNAs in Colorectal Cancer DOI Open Access
Yun Ju Lee, Woo Ryung Kim, Eun Gyung Park

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4548 - 4548

Published: April 21, 2024

Colorectal cancer (CRC) is the third most prevalent to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, remains significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing urgency for effective diagnostic therapeutic approaches. development caused by environmental factors, which mostly lead disruption of signaling pathways. Among these pathways, Wingless/Integrated (Wnt) pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) Mitogen-Activated Protein Kinase (MAPK) Transforming Growth Factor-β (TGF-β) p53 pathway are considered important. These pathways also regulated non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs). They have emerged crucial regulators gene expression in changing their levels. altered patterns ncRNAs been implicated progression development, suggesting potential targets. This review provides an overview five key regulation involved pathogenesis that studied identify promising avenues diagnosis treatment strategies.

Language: Английский

Citations

12
Intrarenal 1-methoxypyrene, an aryl hydrocarbon receptor agonist, mediates progressive tubulointerstitial fibrosis in mice DOI Open Access
Gang Cao, Hua Miao, Yanni Wang

et al.

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 43(11), P. 2929 - 2945

Published: May 16, 2022

Language: Английский

Citations

36
Integrative phosphatidylcholine metabolism through phospholipase A2 in rats with chronic kidney disease DOI Open Access
Yanni Wang, Zhihao Zhang,

Hong-jiao Liu

et al.

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 44(2), P. 393 - 405

Published: Aug. 3, 2022

Language: Английский

Citations

33
Traditional Chinese medicine improved diabetic kidney disease through targeting gut microbiota DOI Creative Commons
Xiaqing Wu, Lei Zhao,

Yanlong Zhao

et al.

Pharmaceutical Biology, Journal Year: 2024, Volume and Issue: 62(1), P. 423 - 435

Published: May 17, 2024

Context Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal that requires replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes ameliorating DKD by addressing the microbiota.

Language: Английский

Citations

8
The Role of Transforming Growth Factor-β (TGF-β) in Asthma and Chronic Obstructive Pulmonary Disease (COPD) DOI Creative Commons
Krzysztof Kraik, Maciej Tota, Julia Laska

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1271 - 1271

Published: July 29, 2024

Asthma and chronic obstructive pulmonary disease (COPD) represent inflammatory respiratory disorders that, despite having distinct pathophysiological underpinnings, both feature airflow obstruction symptoms. A critical component in the pathogenesis of each condition is transforming growth factor-β (TGF-β), a multifunctional cytokine that exerts varying influences across these diseases. In asthma, TGF-β significantly involved airway remodeling, key aspect marked by subepithelial fibrosis, hypertrophy smooth muscle, enhanced mucus production, suppression emphysema development. The facilitates collagen deposition proliferation fibroblasts, which are crucial structural modifications within airways. contrast, role COPD more ambiguous. It initially acts as protective agent, fostering tissue repair curbing inflammation. However, prolonged exposure to environmental factors such cigarette smoke causes signaling malfunction. Such dysregulation leads abnormal excessive deposition, enlargement airspaces, and, thus, accelerated development emphysema. Additionally, epithelial-to-mesenchymal transition (EMT), process contributing phenotypic alterations observed COPD. thorough comprehension multifaceted asthma imperative for elaborating precise therapeutic interventions. We review several promising approaches alter signaling. Nevertheless, additional studies essential delineate further specific mechanisms its potential impacts

Language: Английский

Citations

8
Poria cocos: traditional uses, triterpenoid components and their renoprotective pharmacology DOI

Zhi-yuan Guo,

X. Wu,

Shui-juan Zhang

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Language: Английский

Citations

8