Role of proteases in dysfunctional placental vascular remodelling in preeclampsia

Gutiérrez, Jaime; Gómez, I. Rodríguez; Chiarello, Delia I.; Salsoso, Rocío; Klein, Andrés D.; Guzmán-Gutiérrez, Enrique; Toledo, Fernando; Sobrevía, Luis

doi:10.1016/j.bbadis.2019.04.004

Cited by 14 publications

(11 citation statements)

References 100 publications

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“…Dimethylsulfoxide (DMSO), cells added with DMSO of the same volume; SC79, cells added with 10 µM SC79; LY294002, cells added with 10 µM LY294002. (Graham and McCrae, 1996;Choi et al, 2003;Shokry et al, 2009;Plaks et al, 2013;Gutierrez et al, 2020;Lin et al, 2020). Hereby, we found that galectin-14 promoted the expression and activity of MMP-9 and increased the MMP-9/TIMP-1 ratio while the migration and invasion of trophoblasts were enhanced.…”

Section: Discussionmentioning

confidence: 54%

Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin

Wang

et al. 2021

Front. Cell Dev. Biol.

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Galectin-14 is specifically expressed in placental trophoblasts, and its expression is reduced in trophoblasts retrieved from the cervix of women destined to develop early pregnancy loss. However, the roles of galectin-14 in regulating trophoblasts and in the pathogenesis of pregnancy complication have never been investigated. In the current research, we aimed to investigate the roles of galectin-14 in the regulation of trophoblasts. Tissues of the placenta and villi were collected. Primary trophoblasts and human trophoblast cell line HTR-8/SVneo were used. Western blotting and RT-PCR were used to quantify gene expression. The siRNA-mediated galectin-14 knockdown and lentivirus-mediated overexpression were performed to manipulate the gene expression in trophoblasts. Transwell migration and invasion assays were used to evaluate cell migration and invasion capacity. Gelatin zymography was used to determine the gelatinase activity. Galectin-14 was significantly decreased in the villi of early pregnancy loss and the placenta of preeclampsia. Knockdown of galectin-14 in primary trophoblasts inhibited cell migration and invasion, downregulated the expression of matrix metalloproteinase (MMP)-9 and N-cadherin, the activity of MMP-9, and decreased the phosphorylation of Akt. Meanwhile, the overexpression of galectin-14 in HTR-8/SVneo promoted cell migration and invasion, upregulated the expression of MMP-9 and N-cadherin, the activity of MMP-9, and increased the phosphorylation of Akt. Increased Akt phosphorylation promoted cell migration and invasion and upregulated the expression and activity of MMP-9, while decreased Akt phosphorylation inhibited cell migration and invasion and downregulated the expression and activity of MMP-9. Thus, galectin-14 promotes trophoblast migration and invasion by enhancing the expression of MMP-9 and N-cadherin through Akt phosphorylation. The dysregulation of galectin-14 is involved in the pathogenesis of early pregnancy loss and preeclampsia.

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Section: Discussionmentioning

confidence: 54%

Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Defective trophoblast invasion of the uterus has been reported to be one of the crucial mechanisms of PE. Furthermore, increased oxidative stress and reduced uteroplacental blood flow and oxygen availability were closely associated with reduced trophoblast invasion (24). ANGPTL8 is a newly identified hormone with the ability to regulate the glucose and lipid metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of the effect of angiopoietin‑like protein 8 on the proliferation, invasion and migration of placental trophoblasts in preeclampsia

Wang

Dong-lin

2020

Exp Ther Med

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Preeclampsia (PE) is a pregnancy-specific systemic disorder characterized by various manifestations of organ dysfunction. Inadequate trophoblastic invasion of the uterine wall is involved in the pathogenesis of PE. Angiopoietin-like protein 8 (ANGPTL8) serves an important role in cardiovascular disease development and may have a potential effect on cell proliferation. In the present study, downregulation of ANGPTL8 promoted cell proliferation, decreased p21 expression, and increased the expression levels of cyclin-dependent kinase 2 and proliferating cell nuclear antigen in HTR8/SVneo cells. Silencing of ANGPTL8 led to significant acceleration in cell migration and invasion, and markedly enhanced the matrix metalloproteinase (MMP)-2 and MMP-9 expression levels. In addition, the protein expression levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 were decreased in the group transfected with small interfering RNA (si)-ANGPTL8-1 as compared with those in the control and si-negative control groups. Taken together, these results indicated that ANGPTL8 downregulation promoted the proliferation, migration and invasion of trophoblast cells. Thus, ANGPTL8 suppresses the viability, proliferation, migration and invasion of trophoblast cells, and may be a potential therapeutic target for the clinical treatment of PE.

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“…For example, a decrease of uteroplacental blood flow and oxygen availability associated with an increase of oxidative stress was reported during preeclampsia. Cysteine cathepsins were identified as putative worthy players of the dysfunctional placental vascular remodeling that occurs during preeclampsia [78]. Also, these proteases participate to inflammatory activation, cholesterol metabolism, neovascularization, and cell signaling, as well tissue fibrosis, and contribute to cardiovascular diseases (CVD); among other regulatory factors, cysteine cathepsins are regulated by oxidative stress during the development of CVD (see for review: Reference [79]).…”

Section: Cysteine Cathepsins In Pulmonary Diseasesmentioning

confidence: 99%

Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants

Lalmanach

Saidi

Bigot

et al. 2020

IJMS

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Besides their primary involvement in the recycling and degradation of proteins in endo-lysosomal compartments and also in specialized biological functions, cysteine cathepsins are pivotal proteolytic contributors of various deleterious diseases. While the molecular mechanisms of regulation via their natural inhibitors have been exhaustively studied, less is currently known about how their enzymatic activity is modulated during the redox imbalance associated with oxidative stress and their exposure resistance to oxidants. More specifically, there is only patchy information on the regulation of lung cysteine cathepsins, while the respiratory system is directly exposed to countless exogenous oxidants contained in dust, tobacco, combustion fumes, and industrial or domestic particles. Papain-like enzymes (clan CA, family C1, subfamily C1A) encompass a conserved catalytic thiolate-imidazolium pair (Cys25-His159) in their active site. Although the sulfhydryl group (with a low acidic pKa) is a potent nucleophile highly susceptible to chemical modifications, some cysteine cathepsins reveal an unanticipated resistance to oxidative stress. Besides an introductory chapter and peculiar attention to lung cysteine cathepsins, the purpose of this review is to afford a concise update of the current knowledge on molecular mechanisms associated with the regulation of cysteine cathepsins by redox balance and by oxidants (e.g., Michael acceptors, reactive oxygen, and nitrogen species).

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Role of proteases in dysfunctional placental vascular remodelling in preeclampsia

Cited by 14 publications

References 100 publications

Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin

Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin

Molecular mechanism of the effect of angiopoietin‑like protein 8 on the proliferation, invasion and migration of placental trophoblasts in preeclampsia

Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants

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