scholarly journals A dynamic equilibrium between TTP and CPEB4 controls mRNA stability and inflammation resolution

2021 ◽  
Author(s):  
Clara Suñer ◽  
Annarita Sibilio ◽  
Judit Martín ◽  
Chiara Lara Castellazzi ◽  
Oscar Reina ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mrna Stability ◽  
Regulatory Network ◽  
Dynamic Equilibrium ◽  
Relative Number ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling ◽  
Inflammation Resolution

SUMMARYTemporal control of inflammation is critical to avoid pathological developments, and is largely defined through the differential stabilities of mRNAs. While TTP-directed mRNA deadenylation is known to destabilize ARE-containing mRNAs, this mechanism alone cannot explain the variety of mRNA expression kinetics observed during inflammation resolution. Here we show that inflammation resolution requires CPEB4 expression, in vitro and in vivo. Our results identify that CPEB4-directed polyadenylation and TTP-mediated deadenylation compete during the resolutive phase of the LPS response to uncouple the degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. The outcome of this equilibrium is quantitatively defined by the relative number of CPEs and AREs in each mRNA, and further shaped by the coordinated regulation by the MAPK signalling pathway of the levels and activities of their trans-acting factors, CPEB4 and TTP. Altogether, we describe a temporal- and transcript-specific regulatory network controlling the extent of the inflammatory response.

scholarly journals Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis In Vitro and In Vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Lu ◽  
Yuqi Yang ◽  
Junhong Zhang ◽  
Hongyu Zhang ◽  
Changju Ma ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Umbilical Vein ◽  
Oxidative Status ◽  
Signalling Pathway ◽  
Psoriatic Skin ◽  
Dependent Manner ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.

scholarly journals Isoquercitrin inhibits the progression of liver cancer in vivo and in vitro via the MAPK signalling pathway

2014 ◽  
Vol 31 (5) ◽  
pp. 2377-2384 ◽  
Author(s):  
GUIHONG HUANG ◽  
BO TANG ◽  
KUN TANG ◽  
XIAOMIN DONG ◽  
JUNGANG DENG ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Signalling Pathway ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects

Recombinant TAT-Thymosin β-4 Promotes Angiogenesis by Activating VEGFR2 Signaling Pathway

2021 ◽  
Author(s):  
Chul Min Kim ◽  
Yun-Mi Jeong ◽  
Jae-Hun Kim ◽  
Guolong Jin ◽  
Hyeongkwon Oh ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Signaling Pathway ◽  
Dynamic Equilibrium ◽  
Common Type ◽  
Cell Penetrating Peptide ◽  
Angiogenic Potential ◽  
Angiogenic Effect ◽  
Vegfr2 Signaling

Abstract Thymosin β-4 is a 43-amino acid intracellular polypeptide that was originally isolated from bovine thymus. Of the 16 known thymosin families, thymosin β-4 is the most common type found in all tissues. Thymosin β-4 regulates angiogenesis, cell differentiation, morphogenesis, migration, and organogenesis and is linked to a dynamic equilibrium between G-actin and F-actin. In particular, thymosin β-4 is well-known for its angiogenic and anti-apoptotic functions. In this study, we synthesized thymosin β-4 linked with the well-known cell-penetrating peptide TAT (YGRKKRRRQRRR). TAT-thymosin β-4 promotes angiogenesis and cell migration in vitro via the VEGFR2 signaling pathway and reduces apoptosis. To examine angiogenic potential in vivo, a Matrigel Plus assay was conducted that revealed the angiogenic effect of TAT-thymosin β-4. In conclusion, TAT-thymosin β-4 promotes blood vessels and is expected to be applicable in regenerative medicine for all organs requiring blood vessels.

Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis

2004 ◽  
Vol 286 (2) ◽  
pp. F356-F362 ◽  
Author(s):  
John Kanellis ◽  
Roger Bick ◽  
Gabriela Garcia ◽  
Luan Truong ◽  
Chun Chui Tsao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intracellular Calcium ◽  
In Vivo Studies ◽  
Cellular Processes ◽  
Multiple Organs ◽  
Chemotactic Protein ◽  
Stromal Cell Derived Factor ◽  
Mammalian Counterpart

In macrophages, changes in intracellular calcium have been associated with activation of cellular processes that regulate cell adhesion and motility and are important for the response of macrophages to antigenic stimuli. The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) is expressed in multiple organs including the thymus and spleen, and hence, we hypothesized that it may have a role in modulating the immune/inflammatory response. Using murine macrophage-like (RAW264.7) and human monoblast-like (U937) cells to study chemotaxis in vitro, we found that STC1 attenuated chemokinesis and diminished the chemotactic response to monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α. Consistent with these findings, STC1 blunted the rise in intracellular calcium following MCP-1 stimulation in RAW264.7 cells. In vivo studies suggested differential expression of STC1 in obstructed kidney and localization to macrophages. MCP-1 and STC1 transcripts were both upregulated following ureteric obstruction, suggesting a functional association between the two genes. Our data suggest a role for mammalian STC1 in modulating the immune/inflammatory response.

scholarly journals Uncovering and Engineering a Mini-Regulatory Network of the TetR-Family Regulator SACE_0303 for Yield Improvement of Erythromycin in Saccharopolyspora erythraea

2021 ◽  
Vol 9 ◽  
Author(s):  
Ying Liu ◽  
Sabir Khan ◽  
Panpan Wu ◽  
Bowen Li ◽  
Lanlan Liu ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Target Genes ◽  
Antibacterial Activities ◽  
Saccharopolyspora Erythraea ◽  
High Yield ◽  
Yield Strain ◽  
Yield Improvement ◽  
Erythromycin Production

Erythromycins produced by Saccharopolyspora erythraea have broad-spectrum antibacterial activities. Recently, several TetR-family transcriptional regulators (TFRs) were identified to control erythromycin production by multiplex control modes; however, their regulatory network remains poorly understood. In this study, we report a novel TFR, SACE_0303, positively correlated with erythromycin production in Sac. erythraea. It directly represses its adjacent gene SACE_0304 encoding a MarR-family regulator and indirectly stimulates the erythromycin biosynthetic gene eryAI and resistance gene ermE. SACE_0304 negatively regulates erythromycin biosynthesis by directly inhibiting SACE_0303 as well as eryAI and indirectly repressing ermE. Then, the SACE_0303 binding site within the SACE_0303-SACE_0304 intergenic region was defined. Through genome scanning combined with in vivo and in vitro experiments, three additional SACE_0303 target genes (SACE_2467 encoding cation-transporting ATPase, SACE_3156 encoding a large transcriptional regulator, SACE_5222 encoding α-ketoglutarate permease) were identified and proved to negatively affect erythromycin production. Finally, by coupling CRISPRi-based repression of those three targets with SACE_0304 deletion and SACE_0303 overexpression, we performed stepwise engineering of the SACE_0303-mediated mini-regulatory network in a high-yield strain, resulting in enhanced erythromycin production by 67%. In conclusion, the present study uncovered the regulatory network of a novel TFR for control of erythromycin production and provides a multiplex tactic to facilitate the engineering of industrial actinomycetes for yield improvement of antibiotics.

Sign in / Sign up

Export Citation Format

Share Document