Abstract: FR-PO1198
The Micropeptide LSMEM1 Attenuates Renal Tubulointerstitial Fibrosis by Reducing Lipid Droplet Accumulation
Session Information
- CKD: Mechanisms - 2
October 25, 2024 | 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
- Bai, Xiaoyan, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background
Chronic Kidney Disease (CKD) is a syndrome defined by persistent changes in kidney structure, function, or both, and today the global burden of CKD is increasing.
Regardless of the starting injury or disease, the most common pathological manifestation of CKD is some form of renal fibrosis that eventually progresses to end-stage renal disease (ESRD).
Micropeptides are commonly defined as polypeptides with arelatively arbitrary length of less than 100–150 amino acids (aa) in length.
Evolving evidence suggests that micropeptides regulate a variety of biological processes, and more and more micro-molecule peptides being discovered as technology develops.
In recent years a variety of diseases have detected up-regulation of LSMEM1 which is a micropeptide enriched with 133 amino acids.
Methods
Analysis of renal expression levels of LSMEM1 in CKD patients compared to normal controls using the GEO database and nephroseq database.
Though the immunohistochemical staining, the level of LSMEM1 was examined in patients with CKD caused by different diseases.
In the vivo, We constructed the LSMEM1-knockout mice followed by unilateral ureteral ligation (UUO) surgery and executed the mice 7 days later.
In the vitro, lentivirus was used to silence or over-expression LSMEM1 in HK-2 cells under the TGF-β stimulation.
Other testing methods include RNA-seq, ELISA, Colorimetric Assay, Western Bloting, Masson staining, Sirius Red Staining and et al.
Results
Compared to normal controls, LSMEM1 expression is upregulated in CKD kidneys.
Animal and cellular experiments showed that LSMEM1 expression levels increased with increasing degrees of fibrosis.
Animal experiments showed that renal fibrosis was aggravated in UUO mice after LSMEM1 knockdown compared with the SHAM group.
Cellular experiments showed that silencing LSMEM1 elevated the level of fibrosis induced by TGF-β in HK-2 cells and, conversely, overexpression reduced.
RNA-seq analysis shows lipid metabolism-related pathways are significantly enriched in the kidney of LSMEM1-KO mice.
Knockdown of LSMEM1 caused more severe lipid accumulation in mice and cell, conversely, overexpression attenuated.
Conclusion
Current study suggests the micropeptide LSMEM1 could attenuates renal tubulointerstitial fibrosis by reducing lipid droplet accumulation and may be a therapeutic target in CKD.