scholarly journals Cell-state specific aggresome formation in fibroblasts is driven by stress-activated MAPK signaling

2021 ◽  
Author(s):  
Christopher S. Morrow ◽  
Zachary P. Arndt ◽  
Bo Peng ◽  
Eden Y. Zewdie ◽  
Bérénice A. Benayoun ◽  
...  
Keyword(s):  
Proteasome Inhibition ◽  
Fibroblast Cell ◽  
Mapk Signaling ◽  
Dermal Fibroblasts ◽  
Specific Response ◽  
Cell State ◽  
Distinct Cell ◽  
Aggresome Formation ◽  
Immortalized Cell ◽  
Universal Protein

The aggresome is a protein turnover system in which proteins are trafficked along microtubules to the centrosome for degradation. Despite extensive focus on aggresomes in immortalized cell lines, it remains unclear if the aggresome is conserved in all primary cells and all cell-states. Here we examined the aggresome in primary adult mouse dermal fibroblasts in four distinct cell-states. We found that in response to proteasome inhibition, quiescent and immortalized fibroblasts formed aggresomes whereas proliferating and senescent fibroblasts did not. Transcriptomic analysis of the fibroblast cell-state-specific response to proteasome inhibition revealed that stress-activated MAPK signaling was associated with aggresome formation. Supporting a functional role for stress-activated MAPK signaling in aggresome formation, inhibition of TAK1 and p38α/β MAPKs suppressed aggresome formation. Together, our data suggest that the aggresome is a non-universal protein degradation system that forms through stress-activated MAPK signaling which can be used cell-state specifically.

scholarly journals Anticatabolic and Anti-Inflammatory Effects of Myricetin 3-O-β-d-Galactopyranoside in UVA-Irradiated Dermal Cells via Repression of MAPK/AP-1 and Activation of TGFβ/Smad

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1331 ◽  
Author(s):  
Jung Hwan Oh ◽  
Fatih Karadeniz ◽  
Jung Im Lee ◽  
So Young Park ◽  
Youngwan Seo ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
Mapk Signaling ◽  
Skin Aging ◽  
In Vitro Models ◽  
Dermal Fibroblasts ◽  
Hacat Keratinocytes ◽  
Smad Pathway ◽  
Collagen Production ◽  
Induced Changes

UV irradiation is one of the main causes of extrinsic skin aging. UV-mediated skin aging, also known as photoaging, causes excessive breakdown of extracellular matrix which leads skin to lose its elasticity and strength. Several phytochemicals are known to exert anti-photoaging effects via different mechanisms, partly due to their antioxidant properties. The current study has been carried out to determine the potential anti-photoaging properties of myricetin 3-O-β-d-galacto-pyranoside (M3G), a flavonol glycoside isolated from L. tetragonum, in UVA-irradiated in vitro models; HaCaT keratinocytes and human dermal fibroblasts (HDFs). UVA-induced changes in MMP-1 and collagen production have been observed in HaCaT keratinocytes and HDFs. Further, UVA-induced activation of MAPK signaling, and pro-inflammatory cytokine production have been investigated. TGFβ/Smad pathway has also been analyzed in UVA-irradiated HDFs. Treatment with M3G reversed the UVA-induced changes in MMP-1 and collagen production both in HaCaT keratinocytes and HDFs. UVA-mediated activation of p38, ERK and JNK MAPK activation was also inhibited by M3G treatment in HaCaT keratinocytes. In HDFs, M3G was able to upregulate the TGFβ/Smad pathway activation. In addition, M3G downregulated the UVA-induced pro-inflammatory cytokines in keratinocytes and HDFs. It has been suggested that the M3G has exerted potential antiphotoaging properties in vitro, by attenuating UVA-induced changes in MMP-1 and collagen production in keratinocytes and dermal fibroblasts.

scholarly journals Wound Healing Potential of Spirulina Protein on CCD-986sk Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 130
Author(s):  
Ping Liu ◽  
Jeong-Wook Choi ◽  
Min-Kyeong Lee ◽  
Youn-Hee Choi ◽  
Taek-Jeong Nam
Keyword(s):  
Wound Healing ◽  
Dermal Fibroblast ◽  
Fibroblast Cell ◽  
Underlying Mechanism ◽  
Human Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Cyclin Dependent Kinase ◽  
Pi3k Inhibitor Ly294002 ◽  
And Migration ◽  
Proliferation And Migration

Wound healing is a dynamic and complex process. The proliferation and migration of dermal fibroblasts are crucial for wound healing. Recent studies have indicated that the extracts from Spirulina platensis have a positive potential for wound healing. However, its underlying mechanism is not fully understood. Our previous study showed that spirulina crude protein (SPCP) promoted the viability of human dermal fibroblast cell line (CCD-986sk cells). In this study, we further investigated the wound healing effect and corresponding mechanisms of SPCP on CCD-986sk cells. Bromodeoxyuridine (BrdU) assay showed that SPCP promoted the proliferation of CCD-986sk cells. The wound healing assay showed that SPCP promoted the migration of CCD-986sk cells. Furthermore, cell cycle analysis demonstrated that SPCP promoted CCD-986sk cells to enter S and G2/M phases from G0/G1 phase. Western blot results showed that SPCP significantly upregulated the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 (Cdk2), cyclin-dependent kinase 4 (Cdk4), and cyclin-dependent kinase 6 (Cdk6), as well as inhibited the expression of CDK inhibitors p21 and p27 in CCD-986sk cells. In the meanwhile, SPCP promoted the phosphorylation and activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). However, the phosphorylation of Akt was significantly blocked by PI3K inhibitor (LY294002), which in turn reduced the SPCP-induced proliferation and migration of CCD-986sk cells. Therefore, the results presenting in this study suggested that SPCP can promote the proliferation and migration of CCD-986sk cells; the PI3K/Akt signaling pathway play a positive and important role in these processes.

scholarly journals Resolvin D1 Suppresses H2O2-Induced Senescence in Fibroblasts by Inducing Autophagy through the miR-1299/ARG2/ARL1 Axis

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1924
Author(s):  
Hyun Ji Kim ◽  
Boram Kim ◽  
Hyung Jung Byun ◽  
Lu Yu ◽  
Tuan Minh Nguyen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cellular Senescence ◽  
Vascular Endothelial Cells ◽  
Dermal Fibroblast ◽  
Fibroblast Cell ◽  
Dermal Fibroblasts ◽  
Vascular Endothelial ◽  
Yeast Two Hybrid ◽  
Resolvin D1 ◽  
Two Hybrid

ARG2 has been reported to inhibit autophagy in vascular endothelial cells and keratinocytes. However, studies of its mechanism of action, its role in skin fibroblasts, and the possibility of promoting autophagy and inhibiting cellular senescence through ARG2 inhibition are lacking. We induced cellular senescence in dermal fibroblasts by using H2O2. H2O2-induced fibroblast senescence was inhibited upon ARG2 knockdown and promoted upon ARG2 overexpression. The microRNA miR-1299 suppressed ARG2 expression, thereby inhibiting fibroblast senescence, and miR-1299 inhibitors promoted dermal fibroblast senescence by upregulating ARG2. Using yeast two-hybrid assay, we found that ARG2 binds to ARL1. ARL1 knockdown inhibited autophagy and ARL1 overexpression promoted it. Resolvin D1 (RvD1) suppressed ARG2 expression and cellular senescence. These data indicate that ARG2 stimulates dermal fibroblast cell senescence by inhibiting autophagy after interacting with ARL1. In addition, RvD1 appears to promote autophagy and inhibit dermal fibroblast senescence by inhibiting ARG2 expression. Taken together, the miR-1299/ARG2/ARL1 axis emerges as a novel mechanism of the ARG2-induced inhibition of autophagy. Furthermore, these results indicate that miR-1299 and pro-resolving lipids, including RvD1, are likely involved in inhibiting cellular senescence by inducing autophagy.

scholarly journals CellTrans: An R Package to Quantify Stochastic Cell State Transitions

2017 ◽  
Vol 11 ◽  
pp. 117793221771224 ◽  
Author(s):  
Thomas Buder ◽  
Andreas Deutsch ◽  
Michael Seifert ◽  
Anja Voss-Böhme
Keyword(s):  
Cell Lines ◽  
Transition Probabilities ◽  
Cell Lineage ◽  
R Package ◽  
State Transitions ◽  
Cell State ◽  
Current State ◽  
Cancerous Cell ◽  
Distinct Cell ◽  
A Cell

Many normal and cancerous cell lines exhibit a stable composition of cells in distinct states which can, e.g., be defined on the basis of cell surface markers. There is evidence that such an equilibrium is associated with stochastic transitions between distinct states. Quantifying these transitions has the potential to better understand cell lineage compositions. We introduce CellTrans, an R package to quantify stochastic cell state transitions from cell state proportion data from fluorescence-activated cell sorting and flow cytometry experiments. The R package is based on a mathematical model in which cell state alterations occur due to stochastic transitions between distinct cell states whose rates only depend on the current state of a cell. CellTrans is an automated tool for estimating the underlying transition probabilities from appropriately prepared data. We point out potential analytical challenges in the quantification of these cell transitions and explain how CellTrans handles them. The applicability of CellTrans is demonstrated on publicly available data on the evolution of cell state compositions in cancer cell lines. We show that CellTrans can be used to (1) infer the transition probabilities between different cell states, (2) predict cell line compositions at a certain time, (3) predict equilibrium cell state compositions, and (4) estimate the time needed to reach this equilibrium. We provide an implementation of CellTrans in R, freely available via GitHub ( https://github.com/tbuder/CellTrans ).

scholarly journals Regulators of cardiac fibroblast cell state

2020 ◽  
Vol 91-92 ◽  
pp. 117-135 ◽  
Author(s):  
Ross Bretherton ◽  
Darrian Bugg ◽  
Emily Olszewski ◽  
Jennifer Davis
Keyword(s):  
Fibroblast Cell ◽  
Cardiac Fibroblast ◽  
Cell State
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