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Updated: Oct 16, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
YAP1 promotes high glucose-induced inflammation and extracellular matrix deposition in glomerular mesangial cells by
Yan Wang1, Jinmei Xu1, Zhifeng Cheng1
1Department of Endocrinology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Abstract:
Diabetic nephropathy (DN) is one of the most serious microvascular complications of late-stage diabetes. Glomerular mesangial cell (GMC) proliferation and excessive extracellular matrix (ECM) deposition are the main pathological characteristics associated with the occurrence and development of DN. Yes-associated protein 1 (YAP1) can bind to several transcription factors and is associated with the development of various diseases. However, the effects of YAP1 on DN remain unclear. The aim of the present study was to explore the regulatory effect and potential mechanism of YAP1 in glucose-induced inflammation and ECM deposition in high-glucose-treated GMCs. In the present study, HBZY-1 cell models treated with high glucose were constructed, and the effects of YAP1 on the proliferation, inflammation, ECM deposition and fibrosis of HBZY-1 cells were detected. The results showed that YAP1 was highly expressed in HBZY-1 cells treated with high glucose and that YAP1 silencing decreased cell viability, the levels of inflammatory cytokines, ECM deposition and the degree of fibrosis in cells. Further experiments revealed that NF-κB/Jumonji domain-containing protein D3 (JMJD3) signaling pathway inhibitors alleviated the promoting effect of YAP1 overexpression on inflammatory response and ECM deposition in HBZY-1 cells treated with high glucose. In conclusion, it was demonstrated that YAP1 can promote high glucose-induced inflammation and ECM deposition by activating the NF-κB/JMJD3 signaling pathway in GMCs.
Insights
Yes-associated protein 1 (YAP1) promotes diabetic nephropathy by increasing inflammation and extracellular matrix deposition in kidney cells. YAP1 activates the NF-κB/JMJD3 pathway, contributing to diabetic nephropathy progression.
Area of Science:
- Nephrology
- Molecular Biology
- Endocrinology
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) deposition.
- The role of Yes-associated protein 1 (YAP1) in the pathogenesis of DN is not well understood.
Purpose of the Study:
- To investigate the regulatory effect and mechanism of YAP1 in high-glucose-induced inflammation and ECM deposition in GMCs.
Main Methods:
- Established high-glucose-treated HBZY-1 cell models.
- Assessed the impact of YAP1 on cell proliferation, inflammation, ECM deposition, and fibrosis.
- Investigated the involvement of the NF-κB/Jumonji domain-containing protein D3 (JMJD3) signaling pathway.
Main Results:
- YAP1 expression was elevated in high-glucose-treated HBZY-1 cells.
- YAP1 silencing reduced cell viability, inflammatory cytokine levels, ECM deposition, and fibrosis.
- Inhibitors of the NF-κB/JMJD3 pathway attenuated YAP1's pro-inflammatory and pro-fibrotic effects.
Conclusions:
- YAP1 promotes high glucose-induced inflammation and ECM deposition in GMCs.
- This promotion occurs via the activation of the NF-κB/JMJD3 signaling pathway.
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