microRNA-155 Modulates Hepatic Stellate Cell Proliferation, Apoptosis, and Cell Cycle Progression in Rats With Alcoholic Hepatitis via the MAPK Signaling Pathway Through Targeting SOCS1

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

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The Role of EGFR/PI3K/Akt/cyclinD1 Signaling Pathway in Acquired Middle Ear Cholesteatoma

Mediators of Inflammation ◽

10.1155/2013/651207 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Wei Liu ◽

Hongmiao Ren ◽

Jihao Ren ◽

Tuanfang Yin ◽

Bing Hu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathways ◽

Signaling Pathway ◽

External Auditory Canal ◽

Cell Cycle Progression ◽

Critical Role ◽

Immunohistochemical Method ◽

Cycle Progression ◽

Middle Ear Cholesteatoma

Cholesteatoma is a benign keratinizing and hyper proliferative squamous epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of the most important cytokines which has been shown to play a critical role in cholesteatoma. In this investigation, we studied the effects of EGF on the proliferation of keratinocytes and EGF-mediated signaling pathways underlying the pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium by immunohistochemical method. Furthermore,in vitrostudies were performed to investigate EGF-induced downstream signaling pathways in primary external auditory canal keratinocytes (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma epithelium were significantly increased when compared with those of control subjects. We also demonstrated that EGF led to the activation of the EGFR/PI3K/Akt/cyclinD1 signaling pathway, which played a critical role in EGF-induced cell proliferation and cell cycle progression of EACKs. Both EGFR inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced EGFR/PI3K/Akt/cyclinD1 signaling pathway concomitantly with inhibition of cell proliferation and cell cycle progression of EACKs. Taken together, our data suggest that the EGFR/PI3K/Akt/cyclinD1 signaling pathway is active in cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper-proliferation. This study will facilitate the development of potential therapeutic targets for intratympanic drug therapy for cholesteatoma.

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Glucagon-like peptide-1 receptor agonists inhibit hepatic stellate cell activation by blocking the p38 MAPK signaling pathway

Genetics and Molecular Research ◽

10.4238/2015.december.29.17 ◽

2015 ◽

Vol 14 (4) ◽

pp. 19087-19093 ◽

Cited By ~ 5

Author(s):

L.K. Wu ◽

Y.C. Liu ◽

L.L. Shi ◽

K.D. Lu

Keyword(s):

Signaling Pathway ◽

P38 Mapk ◽

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Hepatic Stellate Cell Activation ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000485759 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1616-1628 ◽

Cited By ~ 7

Author(s):

Xin Jin ◽

Er Nie ◽

Xu Zhou ◽

Ailiang Zeng ◽

Tianfu Yu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Colony Formation ◽

Cell Cycle Progression ◽

Malignant Gliomas ◽

Treatment Strategies ◽

Cycle Progression ◽

Glioma Growth

Background: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. Methods: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. Results: We found that follistatin-like 1 (Fstl1) was upregulated in high-grade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. Conclusion: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies.

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