Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle.
10.1097/CM9.0000000000001893
- VernacularTitle:Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle
- Author:
Keke LI
1
;
Jingkai XU
1
;
Ke XUE
1
;
Ruixing YU
1
;
Chengxu LI
1
;
Wenmin FEI
1
;
Xiaoli NING
1
;
Yang HAN
1
;
Ziyi WANG
1
;
Jun SHU
2
;
Yong CUI
1
Author Information
1. Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China.
2. Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 100029, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis/genetics*;
Cell Division;
Humans;
Jurkat Cells;
Lupus Erythematosus, Systemic/genetics*;
RNA, Small Interfering/genetics*
- From:
Chinese Medical Journal
2022;135(4):447-455
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.
METHODS:Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).
RESULTS:TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.
CONCLUSION:TPCN2 might be a potential protective factor against SLE.
