Abstract: FR-PO1208
Peroxisome Proliferator-Activated Receptor (PPAR) Signaling-Mediated Lipid Metabolic Regulation by Micropeptide LSMEM1 Attenuates Renal Pathophysiology
Session Information
- CKD: Mechanisms, AKI, and Beyond - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Liu, Peimin, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Yang, Shanzhi, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Zhang, Hong, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Xu, Haosen, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Jiang, Huan, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Li, Jiaoqing, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Wu, Danfeng, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Bai, Xiaoyan, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background
(1) Small proteins or micropeptides play an important role in disease occurrence, cell signaling and metabolic regulation. (2) We aim to elucidate the function of the small protein LSMEM1 and dissect its implications in CKD.
Methods
(1) Patients: Analyzed LSMEM1 expression/localization in CKD patients via IHC/IF. Correlated LSMEM1 levels with BUN/Cre using ImageJ. (2) scRNA-seq: Identified LSMEM1-associated DEGs and biological processes. (3) In vivo/vitro: Assessed LSMEM1 expression in mice, generated KO/OE models, and investigated its role in DKD using RT-qPCR, WB, TSA, ELISA, Co-IP, etc.
Results
(A) Nephroseq/GEO database analysis revealed predominant renal cortical LSMEM1 localization and elevated mRNA levels in CKD patients. (B) LSMEM1 was significantly upregulated in CKD patients and mouse models (db/db, STZ, UUO, FA) via RT-qPCR/WB/IHC. (C) LSMEM1 levels positively correlated with Scr/BUN. (D) Multiplex IF confirmed LSMEM1 localization in PT cells and podocytes. (E) scRNA-seq showed enrichment in energy/lipid metabolism pathways (PPAR signaling, fatty acid degradation, peroxisome function topping the list). (F) Lsmem1-KO increased serum/kidney TG, TC, LDL but decreased HDL. (G) Venn analysis of PPAR/peroxisome pathways identified SLC27A2 (as known as FATP2). (H) AAV-overexpression-LSMEM1 was injected in mice; lentiviral-silencing/overexpression used in podocytes/PT cells in vitro.
Conclusion
The micropeptide LSMEM1 retards disease progression by reducing the PPAR signaling -mediated lipid droplet accumulation and may be a therapeutic target in CKD.
Funding
- Government Support – Non-U.S.