Activin A as a Novel Chemokine Induces Migration of L929 Fibroblasts by ERK Signaling in Microfluidic Devices

Jiang, Lingling; Qi, Yan; Kong, Xianghan; Wang, Runnan; Qi, Jianfei; Lin, Francis; Cui, Xueling; Liu, Zhonghui

doi:10.3389/fcell.2021.660316

Cited by 9 publications

(7 citation statements)

References 49 publications

(52 reference statements)

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“…In this study, we found that FST significantly enhanced the calcium signal of d‐MESCs, while activin A neutralized FST action on calcium flux. Previous study has also shown that activin A can promote the migration of L929 cells and breast cancer cells through calcium pathway 28,29 . Our data support the conjecture that FST might induce migration of d‐MESCs through increasing calcium influx.…”

Section: Discussionsupporting

confidence: 90%

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling

Liu

et al. 2022

J Cellular Molecular Medi

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Follistatin (FST) and activin A as gonadal proteins exhibit opposite effects on folliclestimulating hormone (FSH) release from pituitary gland, and activin A-FST system is involved in regulation of decidualization in reproductive biology. However, the roles of FST and activin A in migration of decidualized endometrial stromal cells are not well characterized. In this study, transwell chambers and microfluidic devices were used to assess the effects of FST and activin A on migration of decidualized mouse endometrial stromal cells (d-MESCs). We found that compared with activin A, FST exerted more significant effects on adhesion, wound healing and migration of d-MESCs.Similar results were also seen in the primary cultured decidual stromal cells (DSCs) from uterus of pregnant mouse. Simultaneously, the results revealed that FST increased calcium influx and upregulated the expression levels of the migration-related proteins MMP9 and Ezrin in d-MESCs. In addition, FST increased the level of phosphorylation of JNK in d-MESCs, and JNK inhibitor AS601245 significantly attenuated FST action on inducing migration of d-MESCs. These data suggest that FST, not activin A in activin A-FST system, is a crucial chemoattractant for migration of d-MESCs by JNK signalling to facilitate the successful uterine decidualization and tissue remodelling during pregnancy.

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Section: Discussionsupporting

confidence: 90%

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling

Liu

et al. 2022

J Cellular Molecular Medi

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“…Indeed, data on the regulation of several non-canonical pathways by activin A are emerging, similarly to that seen with TGFβ1, with the specific pathway involved depending on cell type and stimulus. In addition to activation of MRTF-A, activin A was also shown in cardiac fibroblasts and a mouse fibroblast cell line to regulate cell proliferation and differentiation through the mitogen activated protein kinases p38 and extracellular signal-regulated kinases 1/2 (ERK1/2) [ 38 , 39 ]. In ovarian cancer cells, the activin A migratory effect was dependent on Akt, Erk and Rac1 activation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

A therapeutic target for CKD: activin A facilitates TGFβ1 profibrotic signaling

Soomro

Khajehei

et al. 2023

Cell Mol Biol Lett

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Background TGFβ1 is a major profibrotic mediator in chronic kidney disease (CKD). Its direct inhibition, however, is limited by adverse effects. Inhibition of activins, also members of the TGFβ superfamily, blocks TGFβ1 profibrotic effects, but the mechanism underlying this and the specific activin(s) involved are unknown. Methods Cells were treated with TGFβ1 or activins A/B. Activins were inhibited generally with follistatin, or specifically with neutralizing antibodies or type I receptor downregulation. Cytokine levels, signaling and profibrotic responses were assessed with ELISA, immunofluorescence, immunoblotting and promoter luciferase reporters. Wild-type or TGFβ1-overexpressing mice with unilateral ureteral obstruction (UUO) were treated with an activin A neutralizing antibody. Results In primary mesangial cells, TGFβ1 induces secretion primarily of activin A, which enables longer-term profibrotic effects by enhancing Smad3 phosphorylation and transcriptional activity. This results from lack of cell refractoriness to activin A, unlike that for TGFβ1, and promotion of TGFβ type II receptor expression. Activin A also supports transcription through regulating non-canonical MRTF-A activation. TGFβ1 additionally induces secretion of activin A, but not B, from tubular cells, and activin A neutralization prevents the TGFβ1 profibrotic response in renal fibroblasts. Fibrosis induced by UUO is inhibited by activin A neutralization in wild-type mice. Worsened fibrosis in TGFβ1-overexpressing mice is associated with increased renal activin A expression and is inhibited to wild-type levels with activin A neutralization. Conclusions Activin A facilitates TGFβ1 profibrotic effects through regulation of both canonical (Smad3) and non-canonical (MRTF-A) signaling, suggesting it may be a novel therapeutic target for preventing fibrosis in CKD.

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“…Activin A induces invasion of human trophoblasts by up-regulating N-Cadherin expression in a Smad3-dependent manner [ 16 ], and increases snail-mediated MMP2 expression through ALK4 [ 50 ]. Mitogen-activated protein kinases (MAPK) signaling pathway involves p38 mitogen-activated protein kinases (p38-MARK) [ 51 ], extracellular signal-regulated kinases 1 and 2 (ERK1/2) [ 52 , 53 ], and c-Jun NH2-terminal kinase (JNK) in a cell type-specific manner [ 54 ]. These signaling proteins can transduce extracellular signals from the activin A ligand to the nucleus to cause the corresponding cell biological effects such as cell proliferation, apoptosis, differentiation, and migration.…”

Section: Discussionmentioning

confidence: 99%

Follistatin Is a Novel Chemoattractant for Migration and Invasion of Placental Trophoblasts of Mice

Yang

et al. 2022

Cells

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Follistatin (FST) as a gonadal protein is central to the establishment and maintenance of pregnancy. Trophoblasts’ migration and invasion into the endometrium are critical events in placental development. This study aimed to elucidate the role of FST in the migration and invasion of placental trophoblasts of mice. We found that FST increased the vitality and proliferation of primary cultured trophoblasts of embryonic day 8.5 (E8.5) mice and promoted wound healing of trophoblasts. Moreover, FST significantly induced migration of trophoblasts in a microfluidic device and increased the number of invasive trophoblasts by Matrigel-coated transwell invasion assay. Being treated with FST, the adhesion of trophoblasts was inhibited, but intracellular calcium flux of trophoblasts was increased. Western blotting results showed that FST had no significant effects on the level of p-Smad3 or the ratio of p-Smad3/Smad3 in trophoblasts. Interestingly, FST elevated the level of p-JNK; the ratio of p-JNK/JNK; and expression of migration-related proteins N-cadherin, vimentin, ezrin and MMP2 in trophoblasts. Additionally, the migration of trophoblasts and expression of N-cadherin, vimentin, and MMP2 in trophoblasts induced by FST were attenuated by JNK inhibitor AS601245. These findings suggest that the elevated FST in pregnancy may act as a chemokine to induce trophoblast migration and invasion through the enhanced JNK signaling to maintain trophoblast function and promote placental development.

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Activin A as a Novel Chemokine Induces Migration of L929 Fibroblasts by ERK Signaling in Microfluidic Devices

Cited by 9 publications

References 49 publications

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling

A therapeutic target for CKD: activin A facilitates TGFβ1 profibrotic signaling

Follistatin Is a Novel Chemoattractant for Migration and Invasion of Placental Trophoblasts of Mice

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