Tissue inhibitors of metalloproteinases are proteolytic targets of matrix metalloproteinase 9

Coates-Park, Sasha; Lazaroff, Carolyn; Gurung, Sadeechya; Rich, Josh; Colladay, Alexandra; O'Neill, Maura; Butler, Georgina S.; Overall, Christopher M.; Stetler-Stevenson, William G.; Peeney, David

doi:10.1016/j.matbio.2023.09.002

Cited by 8 publications

(1 citation statement)

References 59 publications

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“…Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of MMPs, which are enzymes that play central roles in the degradation of ECM components. Among them, TIMP2 can directly bind to MMP2 and is expressed at 10-fold higher levels than TIMP1 and TIMP3 ( 30 , 31 ). Intriguingly, in the context of mechanical stretching, the expression of MMPs and the enzymatic activity of MMP2 were significantly increased in the HVFs of patients with POP.…”

Section: Biomechanical-biochemical Coupling Of Fibroblasts In Popmentioning

confidence: 99%

Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

Wu,

Zhang,

et al. 2024

Front. Med.

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Pelvic organ prolapse (POP) is a significant contributor to hysterectomy among middle-aged and elderly women. However, there are challenges in terms of dedicated pharmaceutical solutions and targeted interventions for POP. The primary characteristics of POP include compromised mechanical properties of uterine ligaments and dysfunction within the vaginal support structure, often resulting from delivery-related injuries. Fibroblasts secrete extracellular matrix, which, along with the cytoskeleton, forms the structural foundation that ensures proper biomechanical function of the fascial system. This system is crucial for maintaining the anatomical position of each pelvic floor organ. By systematically exploring the roles and mechanisms of biomechanical-biochemical transformations in POP, we can understand the impact of forces on the injury and repair of these organs. A comprehensive analysis of the literature revealed that the extracellular matrix produced by fibroblasts, as well as their cytoskeleton, undergoes alterations in patient tissues and cellular models of POP. Additionally, various signaling pathways, including TGF-β1/Smad, Gpx1, PI3K/AKT, p38/MAPK, and Nr4a1, are implicated in the biomechanical-biochemical interplay of fibroblasts. This systematic review of the biomechanical-biochemical interplay in fibroblasts in POP not only enhances our understanding of its underlying causes but also establishes a theoretical foundation for future clinical interventions.

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Section: Biomechanical-biochemical Coupling Of Fibroblasts In Popmentioning

confidence: 99%

Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

Wu,

Zhang,

et al. 2024

Front. Med.

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Unraveling the significance of AGPAT4 for the pathogenesis of endometriosis via a multi-omics approach

Chen,

Shen,

et al. 2024

Hum. Genet.

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Endometriosis is characterized by the ectopic proliferation of endometrial cells, posing considerable diagnostic and therapeutic challenges. Our study investigates AGPAT4’s involvement in endometriosis pathogenesis, aiming to unveil new therapeutic targets. Our investigation by analyzing eQTL data from GWAS for preliminary screening. Subsequently, within the GEO dataset, we utilized four machine learning algorithms to precisely identify risk-associated genes. Gene validity was confirmed through five Mendelian Randomization methods. AGPAT4 expression was measured by Single-Cell Analysis, ELISA and immunohistochemistry. We investigated AGPAT4’s effect on endometrial stromal cells using RNA interference, assessing cell proliferation, invasion, and migration with CCK8, wound-healing, and transwell assays. Protein expression was analyzed by western blot, and AGPAT4 interactions were explored using AutoDock. Our investigation identified 11 genes associated with endometriosis risk, with AGPAT4 and COMT emerging as pivotal biomarkers through machine learning analysis. AGPAT4 exhibited significant upregulation in both ectopic tissues and serum samples from patients with endometriosis. Reduced expression of AGPAT4 was observed to detrimentally impact the proliferation, invasion, and migration capabilities of endometrial stromal cells, concomitant with diminished expression of key signaling molecules such as Wnt3a, β-Catenin, MMP-9, and SNAI2. Molecular docking analyses further underscored a substantive interaction between AGPAT4 and Wnt3a.Our study highlights AGPAT4’s key role in endometriosis, influencing endometrial stromal cell behavior, and identifies AGPAT4 pathways as promising therapeutic targets for this condition.

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Unveiling the bidirectional role of MMP9: A key player in kidney injury

Pang,

Ye,

Jiang

et al. 2024

Cellular Signalling

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Tissue inhibitors of metalloproteinases are proteolytic targets of matrix metalloproteinase 9

Cited by 8 publications

References 59 publications

Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

Unraveling the significance of AGPAT4 for the pathogenesis of endometriosis via a multi-omics approach

Unveiling the bidirectional role of MMP9: A key player in kidney injury

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