Research progress on molecular mechanism of transcription factor C/EBPβ in lung diseases / 中华危重病急救医学

CCAAT enhancer binding protein β (C/EBPβ), as a nuclear transcription factor necessary for the development of liver, airway epithelium, and adipose tissue, plays a vital role in physiological processes related to cell proliferation, apoptosis, and differentiation. However, the up-regulation of C/EBPβ activates signal pathways related to inflammatory response, epithelial-mesenchymal transition, cell proliferation and invasion, immune response, and angiogenesis by regulating a series of downstream genes transcription promotes the development of lung diseases. Therefore, targeting C/EBPβ may be a potential treatment strategy for lung diseases. This paper summarizes the regulatory effects of C/EBPβ and related signaling pathways in lung infection, asthma, chronic obstructive pulmonary disease, lung injury, pulmonary fibrosis, and lung cancer to provide a theoretical basis for the precision medicine of lung diseases.

Role of CCAAT/enhancer binding protein β in acute cerebral ischemia / 国际脑血管病杂志

CCAAT/enhancer binding protein β (C/EBPβ), a transcriptional factor of the basic-leucine zipper family, can regulate the transcription activity of downstream target genes. After acute cerebral ischemia, the activity of C/EBPβ changes, and participates in the process of cerebral ischemia injury by regulating neuronal apoptosis and inflammation. This article reviews the molecular biological characteristics of C/EBPβ and its expression changes and role in acute cerebral ischemia, providing a basis for developing new neuroprotective drugs for acute cerebral ischemia using C/EBPβ as therapeutic target.

Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-B/MAPK signaling and protecting chondrocytes

The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1 were administered to chondrocytes. Micro-CT scanning and histological observations were conducted on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IB, which further reduced the downstream phosphorylation of P65 in nuclear factor-B (NF-B) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1-induced chondrocyte damage. , Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.

Senescence-associated secretory phenotype and its complex regulation networks: A review of molecular mechanisms / 第二军医大学学报

Cellular senescence is a state of permanent growth arrest characterized by an irreversible exit from the cell cycle and the secretion of senescence-associated secretory phenotype (SASP). The secretory process of SASP can be roughly divided into three steps: DNA damage response (DDR)-rapid paracrine, early and mature stages. The complex molecular regulation mechanisms of SASP involve DDR, p38 mitogen-activated protein kinase (MAPK) signal pathway, activation of nuclear factor κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), epigenetic alterations of SASP gene, posttranscriptional regulation of gene and autophagy. SASP regulates a variety of pathological states caused by microenvironment changes and has been a drug target to regulate the aging effect, which providing a new therapeutic method for tumor and agerelated pathological states. In this paper, we classified the different types of SASP, reviewed the role of SASP in biological processes and discussed the related molecular mechanisms.

Curcumin inhibits preadipocyte differentiation by reducing CREB transcriptional activity / 中国药理学通报

Aim To investigate the effect of curcumin on differentiation of 3T3-L1 preadipocytes and its mechanism.Methods 3T3-L1 preadipocytes were treated with curcumin at different concentrations (10,20,40 μmol · L-1) and cell differentiation was synergistically induced.The proliferation of 3T3-L1 preadipocytes was detected by MTT assay.The lipid accumulation was detected by oil red O staining method,and the levels of CREB,C/EBPβ,C/EBPα,PPARγmRNA and protein in 3T3-L1 preadipocytes were detected by qRT-PCR and Western blot.Results MTT results showed that curcumin had a significant inhibitory effect on proliferation of 3T3-L1 preadipocytes in a dose-and time-dependent manner.Oil red O staining showed that curcumin inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner.When 0,20,40 μmol · L-1 curcumin treatment of 3T3-L1 preadipocytes were performed,the levels of p-CREB,C/EBPβ,C/EBPα,PPARγ mRNA and protein significantly decreased with the increasing dose of curcumin (P ＜ 0.05).Conclusions Curcumin can effectively inhibit the proliferation and differentiation of 3T3-L1 preadipocytes.The mechanism may be that curcumin inhibits CREB transcriptional activity and inhibits the expression of C/EBPβ,C/EBPα and PPARγ.

Progress on roles and mechanisms of CCAAT/enhancer binding protein β in endometrium decidualization / 上海交通大学学报（医学版）

CCAAT/enhancer binding protein β (C/EBPβ) is a critical member of C/EBP family.C/EBPβ,based on the leucine zipper located in C terminal of the protein,can regulate transcriptional activities of downstream target genes involved in diverse cellular processes,such as proliferation and differentiation.Recently published studies have identified that C/EBPβ is essential in the decidualization of endometrial stromal cells.This review summarizes the roles and mechanisms of C/EBPβ during the courses of decidualization,which is aimed at providing novel insights for dysfunctional decidualization.

Farnesoid X receptor, the bile acid sensing nuclear receptor, in liver regeneration

The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs) are ligands of farnesoid X receptor (FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.

Saikosaponin D inhibits proliferation and induces apoptosis via C/EBPβ-p53 signal pathway in human hepatoma HepG2 cells / 药物分析学报

Objective To investigate the anticancer effects and detailed mechanisms of Saikosaponin D (SSD) in human hepatoma HepG2 cells. Methods Cell proliferation and apoptosis were tested by MTT assay and Annexin-V/PI assay respectively. The expressions of CCAAT enhancer binding protein β(C/EBPβ) and p53 were detected by RT-PCR and Western blotting. Results SSD inhibited cell proliferation in a dose-dependent manner and induced apoptosis at the concentration of 5.0mg/L. SSD significantly increased the mRNA and protein levels of C/EBPβ and p53 in a dose-dependent manner. Conclusion SSD exerts its anticancer effect by inhibiting cell proliferation and inducing apoptosis partly through C/EBPβ-p53 signal pathway in HepG2 cells.