STAT3-mediated MMP-2 expression is required for 15-HETE-induced vascular adventitial fibroblast migration

Zhang, Li; Li, Yumei; Liu, Yu-Mei; Wang, Xiaoyan; Chen, Minggang; Xing, Yan; Zhu, Daling

doi:10.1016/j.jsbmb.2015.01.015

Cited by 19 publications

(35 citation statements)

References 32 publications

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“…The sources of PASMCs may be proliferation or another type of cell transformation. As we previously reported, the adventitial fibroblasts turned into SMCs under hypoxia exposure [2,37]. In this study, we demonstrated that Gal-3 is able to induce conversion of PAECs into VSMCs via an EndMT-like process, which may be important to small pulmonary vessel muscularity in PAH.…”

Section: Discussionsupporting

confidence: 75%

Galectin-3- Mediated Transdifferentiation of Pulmonary Artery Endothelial Cells Contributes to Hypoxic Pulmonary Vascular Remodeling

Zhang

Zeng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Vascular muscularity is a key event in vessel remodeling during pulmonary artery hypertension (PAH). Endothelial-mesenchymal transdifferentiation (EndMT) has been increasingly reported to play a role in disease occurrence. Galectin-3, a carbohydrate-binding protein regulates cell proliferation, differentiation, migration and neovascularization. However, whether galectin-3 controls endothelial cell transdifferentiation during the development of PAH is unknown. Methods: Rats were exposed to normoxic or hypoxic conditions (fraction of inspired O₂ 0.10) for 21 d to establish PAH models. Hemodynamic changes were evaluated through surgery of the right jugular vein and ultrasound biomicroscopy inviVue. And vessel pathological alterations were detected by H&E staining. Galectin-3 (Gal-3)-induced pulmonary artery endothelium cell (PAEC) dynamic alterations were measured by MTT assays, Cell immunofluorescence, Flow cytometry, Real-time PCR and Western blot. Results: Our study demonstrated that Gal-3 was expressed in hypoxic pulmonary vascular adventitia and intima. The increased Gal-3 expression was responsible for hypoxic vessel remodeling and PAH development in vivo. Gal-3 was found to inhibit cell proliferation and apoptosis in cultured endothelial cells. Meanwhile endothelial cell morphology was altered and exhibited smooth muscle-like cell features as demonstrated by the expression of α-SMA after Gal-3 treatment. Gal-3 activated Jagged1/Notch1 pathways and induced MyoD and SRF. When MyoD or SRF were silenced with siRNAs, Gal-3-initiated transdifferentiation in endothelial cells was blocked as indicated by a lack of α-SMA. Conclusion: These results suggest that Gal-3 induces PAECs to acquire an α-SMA phenotype via a transdifferentiation process which depends on the activation of Jagged1/Notch1 pathways that mediate MyoD and SRF expression.

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Section: Discussionsupporting

confidence: 75%

Galectin-3- Mediated Transdifferentiation of Pulmonary Artery Endothelial Cells Contributes to Hypoxic Pulmonary Vascular Remodeling

Zhang

Zeng

et al. 2018

Cell Physiol Biochem

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“…Finally, MMP-2 and MMP-9, which are produced by AFs during arteriogenesis and disease progression and have been shown to play a role in AF phenotype transition and in tissue remodeling in the progression of vascular disease [28, 37], secretion was examined. After 3 days of culture, MMP-2 production by AFs was initially independent of hydrogel modulus, where 128.7–157.5 pg MMP-2/ng DNA was detected for all hydrogel formulations after 3 days of culture (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recent observations indicate that variations in matrix mechanics can regulate fibroblast morphology, proliferation, signaling pathways, and activation, leading to shifts in vascular remodeling [25, 26]. For example, AFs in injured arteries can convert to myofibroblasts [27] and alter the function and structure of the vessel wall by increasing the expression of ECM proteins or proteases, such as matrix metalloproteinases (MMPs) [28]. Similar phenomena have been observed in vitro where several recent studies have confirmed that matrix stiffness significantly impacts the activation of fibroblasts, both initially and over time [10, 29, 30].…”

Section: Introductionmentioning

confidence: 99%

Aortic adventitial fibroblast sensitivity to mitogen activated protein kinase inhibitors depends on substrate stiffness

et al. 2017

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Adventitial fibroblasts (AFs) are key determinants of arterial function and critical mediators of arterial disease progression. The effects of altered stiffness, particularly those observed across individuals during normal vascular function, and the mechanisms by which AFs respond to altered stiffness, are not well understood. To study the effects of matrix stiffness on AF phenotype, cytokine production, and the regulatory pathways utilized to interpret basic cell-matrix interactions, human aortic AFs were grown in 5%, 7.5%, and 10% (w/v%) PEG-based hydrogels with Young’s moduli of 1.2, 3.3, and 9.6 kPa, respectively. In 5% gels, AFs had higher proliferation rates, elevated monocyte chemoattractant protein-1 secretion, and enhanced monocyte recruitment. Significantly more AFs were α-smooth muscle actin positive in 7.5% gels, indicating myofibroblast development. AFs in 10% gels had low proliferation rates but produced high levels of interleukin-6 and vascular endothelial growth factor-A. Importantly, these modulus-dependent changes in AF phenotype were accompanied by alterations in the mitogen-activated protein kinase (MAPK) pathways contributing to the production of cytokines. These data indicate that complex cell regulatory changes occur with altered tissue stiffness and suggest that therapeutics affecting MAPK pathways may have altered effects on AFs depending on substrate stiffness.

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“…As previously described (Zhang et al . , ), rats were exposed to normal and hypoxic environments with fractions of inspired O 2 (FiO 2 ) at 0.21 and 0.12 respectively. Normal control rats were housed in the same room.…”

Section: Methodsmentioning

confidence: 99%

“…H&E staining was used to detect the changes in vessels in the rat lung tissues as previously described (Zhang et al . , ).…”

Section: Methodsmentioning

confidence: 99%

Elk‐1‐mediated 15‐lipoxygenase expression is required for hypoxia‐induced pulmonary vascular adventitial fibroblast dynamics

Zhang

Wang

et al. 2016

Acta Physiologica

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STAT3-mediated MMP-2 expression is required for 15-HETE-induced vascular adventitial fibroblast migration

Cited by 19 publications

References 32 publications

Galectin-3- Mediated Transdifferentiation of Pulmonary Artery Endothelial Cells Contributes to Hypoxic Pulmonary Vascular Remodeling

Galectin-3- Mediated Transdifferentiation of Pulmonary Artery Endothelial Cells Contributes to Hypoxic Pulmonary Vascular Remodeling

Aortic adventitial fibroblast sensitivity to mitogen activated protein kinase inhibitors depends on substrate stiffness

Elk‐1‐mediated 15‐lipoxygenase expression is required for hypoxia‐induced pulmonary vascular adventitial fibroblast dynamics

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