Cited by 66Advanced Glycation End Products researchChronic Kidney Disease and DiabetesTGF-β signaling in diseases

HMGB1 Enhances the AGE-Induced Expression of CTGF and TGF-β via RAGE-Dependent Signaling in Renal Tubular Epithelial Cells

Cheng, Meichu, Liu, Hong, Zhang, Dongshan, Liu, Yinghong, Wang, Chang, Liu, Fuyou, Chen, Junxiang·2015·American Journal of Nephrology

Abstract

Background/Aims: Advanced glycation end products (AGEs) induce epithelial mesenchymal transition (EMT) in renal proximal tubular epithelial cells (PTECs) by promoting the two EMT regulators, transforming growth factor beta (TGF-β) and connective tissue growth factor (CTGF). However, the exact signaling mechanism remains largely unclear. Methods: We investigated the promotion to high mobility group box 1 (HMGB1) in renal tubular epithelial HK-2 cells by AGE-BSA with quantitative PCR and western blot assay, and then determined the regulatory role of HMGB1 in the AGE-BSA-induced CTGF and TGF-β. In addition, the dependence of the receptor of advanced glycation end products (RAGE) was also examined in the CTGF and TGF-β promotion by AGEs and HMGB1 in HK-2 cells using the RNAi method. Results: It was demonstrated that AGEs induced translocation and release of HMGB1 from tubular epithelial HK-2 cells, and the released HMGB1 enhanced the promotion to CTGF and TGF-β by AGEs in HK-2 cells. On the other side, the HMGB1 knockdown by siRNA attenuated the AGE-BSA-induced expression of TGF-β. Moreover, the CTGF and TGF-β promotion in HK-2 cells by AGEs and HMGB1 was RAGE-dependent. Conclusion: Our results indicated that AGEs induced HMGB-1 and promoted the CTGF and TGF-β in renal epithelial HK-2 cells RAGE-dependently. And there was a synergism between AGEs and HMGB1 in the RAGE signaling activation. The in vitro data suggested that the AGE-RAGE and HMGB-1-RAGE signaling might play an important role in the promotion of CTGF and TGF-β in the renal fibrosis process of diabetic nephropathy.

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Crossref · 10.1159/000381464

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  • The AGE-RAGE interaction in the kidney can increase oxidative stress, inflammation, and fibrosis by stimulating CTGF, TGF-β, MAPK, NF-κB and PKC pathways to develop podocyte damage, glomerular hypertrophy, proteinuria, and end-stage renal failure.

    “Similarly, the AGE-RAGE interaction in the kidney can increase oxidative stress, inflammation, and fibrosis by stimulating connective tissue growth factor (CTGF), transforming growth factor-β (TGF-β), MAPK, NF-κB and PKC pathways to develop podocyte damage, glomerular hypertrophy, proteinuria, and ultimately end-stage renal failure66,72,73.”

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Authors
Cheng, M., Liu, H., Zhang, D., Liu, Y., Wang, C., Liu, F., & Chen, J.
Affiliations
Central South University (CN)
Venue
American Journal of Nephrology
Publisher
S. Karger AG
Published
2015
Volume
41
Issue
3
Pages
257-266
ISSN
  • 0250-8095 (ISSN-L)
  • 1421-9670
OpenAlex
W2024306433
Cited by
66
References
45
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 9 · 2016: 9 · 2015: 1
FWCI
7.15
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Nephrology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Xiangya Hospital, Central South University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
HMGB1, advanced glycation end products, RAGE, connective tissue growth factor, TGF-beta, epithelial-mesenchymal transition, renal proximal tubular epithelial cells, HK-2 cells, renal fibrosis, diabetic nephropathy, AGE-RAGE signaling pathway
MeSH terms
Receptor for Advanced Glycation End Products, Cell Line, Epithelial Cells, Humans, Kidney Tubules, Proximal, Signal Transduction, Transforming Growth Factor beta, Glycation End Products, Advanced, HMGB1 Protein, Connective Tissue Growth Factor, Epithelial-Mesenchymal Transition

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