Author response: Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

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LIPOPOLYSACCHARIDE-BINDING PROTEIN MODULATES HEPATIC DAMAGE AND INFLAMMATORY RESPONSE AFTER HEMORRHAGIC SHOCK AND RESUSCITATION.

Shock ◽

10.1097/00024382-200306001-00081 ◽

2003 ◽

Vol 19 (Supplement) ◽

pp. 28 ◽

Cited By ~ 1

Author(s):

M. Lehnert ◽

T. Uehara ◽

B. U. Bradford ◽

H. Lind ◽

Y. H. Paik ◽

...

Keyword(s):

Inflammatory Response ◽

Hemorrhagic Shock ◽

Binding Protein ◽

Hepatic Damage ◽

Lipopolysaccharide Binding Protein ◽

Lipopolysaccharide Binding

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Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose

Bioscience Reports ◽

10.1042/bsr20180767 ◽

2018 ◽

Vol 38 (6) ◽

Author(s):

Yan Chen ◽

Yan-Jun Wang ◽

Ying Zhao ◽

Jin-Cheng Wang

Keyword(s):

Diabetes Mellitus ◽

Inflammatory Response ◽

Mesangial Cells ◽

Binding Protein ◽

The Body ◽

Mrna Levels ◽

Diabetic Mice ◽

Response Element ◽

Tnf Α ◽

Element Binding Protein

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.

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