E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-β1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene

ABSTRACT

The differentiation of cardiac fibroblast to myofibroblast is the key process of cardiac fibrosis. In the study, we aimed to determine the function of E2F Transcription Factor 1 (E2F1) in human cardiac fibroblasts (HCFs) differentiation, search for its downstream genes and elucidate the function of them in HCFs differentiation. As a result, we found that E2F1 was up-regulated in TGF-β1-induced HCFs differentiation. Silencing the expression of E2F1 by siRNA in HCFs, we found that the expression of differentiation-related genes (Collagen-1, α-Smooth muscle actin, and Fibronectin-1) was significantly suppressed, combining with proliferation and migration assay, we determined that HCFs differentiation was decreased. Luciferase report assay and immunoprecipitation proved that the oncogene CCNE2 was a direct target gene of E2F1, overexpression of CCNE2 was found in differentiated HCFs, silencing the expression of CCNE2 by siRNA decreased HCFs differentiation. Our research suggested that E2F1 and its downstream target gene CCNE2 play a vital role in TGF-β1-induced HCFs differentiation, thus E2F1 and CCNE2 may be a potential therapeutic target for cardiac fibrosis.

KEYWORDS:

• Cardiac fibrosis
• E2F1
• CCNE2
• human cardiac fibroblasts
• myocardial infarction

Disclosure statement

There is no potential conflict of interests.

Authors’ contributions

RHL, YYW and SX designed the experiment. JC and ZQ conducted the cell culture, RNA and protein extraction, RHL and BX conducted the rest experiments. RHL, BX, YYW, and SX drafted and revised the manuscript. The author(s) read and approved the final manuscript.

Availability of data and materials

The datasets supporting the conclusions of this article are included within the article and its additional files according to demands of journal. All source documents of datasets are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the grants from National Natural Science Foundation of China (81770339). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.