HMGA1 accelerates vascular smooth muscle cell osteogenic phenotype transdifferentiation by elevating pro-inflammatory cytokine IL-1β transcription in chronic kidney disease.
6 affiliations
- 1Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
- 2Hebei Clinical Research Center for Chronic Kidney Disease, Shijiazhuang, China.
- 3Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Shijiazhuang, China.
- 4Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. [email protected].
- 5Hebei Clinical Research Center for Chronic Kidney Disease, Shijiazhuang, China. [email protected].
- 6Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Shijiazhuang, China. [email protected].
Abstract
Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is recognized as a core pathological process underlying vascular calcification (VC). The inflammatory response contributes to the development of phenotypic switch, yet there is a lack of therapeutic strategies targeting this process. In the current study, we first identified that inflammatory factors are associated with the osteogenic differentiation of VSMCs, and Interleukin-1β (IL-1β) might be a key triggering mediator. Furthermore, elevated levels of IL-1β were observed in the calcified arteries of both VC patients and mice, and this increase was positively correlated with the severity of calcification. In vivo, treatment with the IL-1β pharmacological inhibition Canakinumab alleviated calcification and osteogenic conversion in the aortas of CKD mice. In vitro, overexpression of IL-1β exacerbated calcification and osteogenic differentiation by promoting inflammation in VSMCs, emphasizing the central role of pro-inflammatory factors. Mechanistically, HMGA1 was predicted to be a potential transcription factor of IL-1β. Specifically, HMGA1 directly promoted the expression of IL-1β by binding to its promoter region. Moreover, IL-1β inhibition nullified the pro-calcific effect of HMGA1 on VSMCs calcification and osteogenic differentiation, whereas IL-1β overexpression abolished the protective effect of HMGA1 silence. Finally, VSMC-specific HMGA1 deficiency in mice attenuated CKD-induced aorta calcification. Collectively, our findings reveal a novel transcriptional regulatory mechanism governing IL-1β expression, highlighting the HMGA1/IL-1β axis as a promising therapeutic target for VC in CKD.
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BibTeX
@article{yang2026hmga1,
title = {{HMGA1 accelerates vascular smooth muscle cell osteogenic phenotype transdifferentiation by elevating pro-inflammatory cytokine IL-1β transcription in chronic kidney disease.}},
author = {Binhong Yang and Meijuan Cheng and Jingjing Jin and Kaixing Yan and Haoqi Sun and Xinyue Yang and Yunhui Wu and Qi An and Dongxue Zhang and Lixin Chang and Shenglei Zhang and Yaling Bai and Jinsheng Xu},
journal = {Cell death discovery},
year = {2026},
month = aug,
doi = {10.1038/s41420-026-03271-z},
url = {https://europepmc.org/article/MED/42957632},
note = {CC BY},
}
RIS
TY - JOUR
TI - HMGA1 accelerates vascular smooth muscle cell osteogenic phenotype transdifferentiation by elevating pro-inflammatory cytokine IL-1β transcription in chronic kidney disease.
AU - Binhong Yang
AU - Meijuan Cheng
AU - Jingjing Jin
AU - Kaixing Yan
AU - Haoqi Sun
AU - Xinyue Yang
AU - Yunhui Wu
AU - Qi An
AU - Dongxue Zhang
AU - Lixin Chang
AU - Shenglei Zhang
AU - Yaling Bai
AU - Jinsheng Xu
PY - 2026
DA - 2026/08/04
JO - Cell death discovery
DO - 10.1038/s41420-026-03271-z
UR - https://europepmc.org/article/MED/42957632
AB - Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is recognized as a core pathological process underlying vascular calcification (VC). The inflammatory response contributes to the development of phenotypic switch, yet there is a lack of therapeutic strategies targeting this process. In the current study, we first identified that inflammatory factors are associated with the osteogenic differentiation of VSMCs, and Interleukin-1β (IL-1β) might be a key triggering mediator. Furthermore, elevated levels of IL-1β were observed in the calcified arteries of both VC patients and mice, and this increase was positively correlated with the severity of calcification. In vivo, treatment with the IL-1β pharmacological inhibition Canakinumab alleviated calcification and osteogenic conversion in the aortas of CKD mice. In vitro, overexpression of IL-1β exacerbated calcification and osteogenic differentiation by promoting inflammation in VSMCs, emphasizing the central role of pro-inflammatory factors. Mechanistically, HMGA1 was predicted to be a potential transcription factor of IL-1β. Specifically, HMGA1 directly promoted the expression of IL-1β by binding to its promoter region. Moreover, IL-1β inhibition nullified the pro-calcific effect of HMGA1 on VSMCs calcification and osteogenic differentiation, whereas IL-1β overexpression abolished the protective effect of HMGA1 silence. Finally, VSMC-specific HMGA1 deficiency in mice attenuated CKD-induced aorta calcification. Collectively, our findings reveal a novel transcriptional regulatory mechanism governing IL-1β expression, highlighting the HMGA1/IL-1β axis as a promising therapeutic target for VC in CKD.
SN - 2058-7716
ER -