NF2 Inhibits CMPK2-Driven NLRP3 Inflammasome Activation to Alleviate Podocyte Injury in FSGS.
- 1Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, People's Republic of China.
Abstract
Background & aims
Therapeutic strategies directly targeting podocyte injury in focal segmental glomerulosclerosis (FSGS) are limited. Although NF2 is known to regulate cytoskeletal dynamics and cellular homeostasis, its role in podocyte inflammatory injury and downstream mechanisms remains unclear. This study investigated the function of NF2 and its regulatory relationship with CMPK2 in FSGS.Methods
NF2 expression was assessed in kidney tissues from FSGS patients and experimental models. In vivo and in vitro models were used to evaluate the effects of NF2 modulation on podocyte function. Gain- and loss-of-function approaches examined NF2-CMPK2 interactions and downstream inflammatory signaling pathways.Results
NF2 was predominantly expressed in podocytes and significantly downregulated in kidney tissues from FSGS patients and experimental models. NF2 knockdown in human podocytes upregulated CMPK2, activating the NLRP3 inflammasome and promoting IL-1β release, leading to enhanced inflammatory injury. Conversely, NF2 overexpression suppressed CMPK2, inhibited NLRP3 inflammasome activation, reduced IL-1β production, and alleviated podocyte injury.Conclusion
Our findings indicate that NF2 confers protection against podocyte inflammatory injury, likely via modulation of the CMPK2-NLRP3 inflammasome signaling, pointing to a potential therapeutic target for FSGS.
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BibTeX
@article{yang2026inhibits,
title = {{NF2 Inhibits CMPK2-Driven NLRP3 Inflammasome Activation to Alleviate Podocyte Injury in FSGS.}},
author = {Li Yang and Qinqin Tan and Hui Yin and Lan Qiu and Xindi Zhou and Huimin Jiang and Qing Yang and Han Xiao and Wei Jiang and Xuejun Yang and Qiu Li},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s615100},
url = {https://europepmc.org/article/MED/42968943},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - NF2 Inhibits CMPK2-Driven NLRP3 Inflammasome Activation to Alleviate Podocyte Injury in FSGS.
AU - Li Yang
AU - Qinqin Tan
AU - Hui Yin
AU - Lan Qiu
AU - Xindi Zhou
AU - Huimin Jiang
AU - Qing Yang
AU - Han Xiao
AU - Wei Jiang
AU - Xuejun Yang
AU - Qiu Li
PY - 2026
DA - 2026/10/28
JO - Journal of inflammation research
DO - 10.2147/jir.s615100
UR - https://europepmc.org/article/MED/42968943
AB - Background & aims Therapeutic strategies directly targeting podocyte injury in focal segmental glomerulosclerosis (FSGS) are limited. Although NF2 is known to regulate cytoskeletal dynamics and cellular homeostasis, its role in podocyte inflammatory injury and downstream mechanisms remains unclear. This study investigated the function of NF2 and its regulatory relationship with CMPK2 in FSGS.Methods NF2 expression was assessed in kidney tissues from FSGS patients and experimental models. In vivo and in vitro models were used to evaluate the effects of NF2 modulation on podocyte function. Gain- and loss-of-function approaches examined NF2-CMPK2 interactions and downstream inflammatory signaling pathways.Results NF2 was predominantly expressed in podocytes and significantly downregulated in kidney tissues from FSGS patients and experimental models. NF2 knockdown in human podocytes upregulated CMPK2, activating the NLRP3 inflammasome and promoting IL-1β release, leading to enhanced inflammatory injury. Conversely, NF2 overexpression suppressed CMPK2, inhibited NLRP3 inflammasome activation, reduced IL-1β production, and alleviated podocyte injury.Conclusion Our findings indicate that NF2 confers protection against podocyte inflammatory injury, likely via modulation of the CMPK2-NLRP3 inflammasome signaling, pointing to a potential therapeutic target for FSGS.
SN - 1178-7031
ER -