Antagonistic effects of activin A and TNF-α on the activation of L929 fibroblast cells via Smad3-independent signaling

Abstract

Fibroblasts play an important role in inflammation and tissue fibrosis. Both activin A and TNF-α can activate immune cells, however, the roles and relationship of them in activating fibroblasts in inflammation remain unclear. Here, this study revealed that TNF-α promoted the release of NO and IL-6 by L929 fibroblast cells, but co-treatment with activin A attenuated these effects. In contrast, activin A induced cell migration and increased the production of tissue fibrosis-related TGF-β1 and fibronectin, while TNF-α inhibited these function changes of L929 cells induced by activin A. Moreover, this study revealed that activin A and TNF-α regulated the activities of L929 cells via ERK1/2/MAPK pathway, rather than Smad3-dependent signaling pathway. Taken together, these data indicate that activin A and TNF-α exert mutually antagonistic effects on regulating fibroblasts activities, and the balance between their action may determine the process and outcome of fibroblasts-mediated inflammation.

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

“…* P < 0.05 compared with 0.1% DMSO control group. changes of p-Smad3 level in L929 cells stimulated with activin A (Jiang et al, 2020). As an important second messenger in cells, calcium ion extensively exists in the living organisms and participates in a variety of signaling pathways (Varghese et al, 2019).…”

“…Previous study has demonstrated that activin A does not antagonize TNF-α-induced activation of L929 cells via classical Smad signaling pathway (Jiang et al, 2020). Therefore, in order to determine the signal transduction mechanism of activin A regulating the migration of L929 cells, levels of ERK and p-ERK proteins were examined by Western blotting.…”

“…The aberrant overexpression of activin A is frequently detected in the case of inflammation or tissue injury (Sun et al, 2014;Qi et al, 2021). Although our previous study has reported the antagonistic effects of activin A and TNF-α on fibroblast activation (Jiang et al, 2020), the role of activin A in adhesion and migration of fibroblasts is not well characterized. In the present study, the murine fibroblast cell line L929 was utilized to investigate the effects of activin A on adhesion and migration of fibroblasts.…”

Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?

“…Stimulated myofibroblasts are key cells that produce excessive amounts of type I and III collagen and fibronectin, leading to fibrosis formation. Pathohistological analysis of testicular biopsies obtained in asymptomatic infertile men showed marked interstitial infiltration by immune cells in approximately 30% of cases, coinciding with seminal epithelial loss, lamina propria thickening, and tubular fibrosis [27,28,34,35].…”

Electrically Triggered Drug Delivery from Novel Electrospun Poly(Lactic Acid)/Graphene Oxide/Quercetin Fibrous Scaffolds for Wound Dressing Applications

“…Biomaterial extracts are often employed in biocompatibility assessment in order to assess the eventual irritant effect of potential leachates in contact applications, such as wound healing scaffolds [61]. Fibroblast cells are present in the structure of all organs as one of the main components in loose connective tissue, playing an essential role in the inflammation process involved in wound healing [62]. During acute response, fibroblasts can release interleukin 6 (IL-6), and thus the cytokine production was measured here in The SEM micrographs indicated that the cells have a normal elongated morphology when cultivated on all samples, with the exception of 10%PLA/0.5%GO, 10%PLA/1%GO and 10%PLA/0.5%GO/Q, where the fibroblasts adhered to the fillamentous network of these materials with a round shape.…”