Knockdown of TRIM27 expression suppresses the dysfunction of mesangial cells in lupus nephritis by FoxO1 pathway

Abstract

TRIM27 (tripartite motif‐containing 27) is a member of the TRIM (tripartite motif) protein family and participates in a variety of biological processes. Some research has reported that TRIM27 was highly expressed in certain kinds of carcinoma cells and tissues and played an important role in the proliferation of carcinoma cells. However, whether TRIM27 takes part in the progression of lupus nephritis (LN) especially in cells proliferation remains unclear. Our study revealed that the overexpression of TRIM27 was observed in the kidneys of patients with LN, lupus mice and mesangial cells exposed to LN plasma which correlated with the proliferation of mesangial cells and ECM (extracellular matrix) deposition. Downregulation of TRIM27 expression suppressed the proliferation of mesangial cells and ECM accumulation in MRL/lpr mice and cultured human mesangial cells (HMCs) by regulating the FoxO1 pathway. Furthermore, the overexpression of FoxO1 remarkably decreased HMCs proliferation level and ECM accumulation in LN plasma‐treated HMCs. In addition, the protein kinase B (Akt) signal pathway inhibitor LY294002 significantly reduced the expression of TRIM27 and inhibited the dysfunction of mesangial cells. These above data suggested that TRIM27 mediated abnormal mesangial cell proliferation in kidney of lupus and might be the potential target for treating mesangial cell proliferation of lupus nephritis.

Tripartite motif 27 promotes cardiac hypertrophy via PTEN/Akt/mTOR signal pathways

“…Neonatal rat cardiomyocytes (NRCMs) were prepared as previously described [ 21 ]. Briefly, SD rat pups on postnatal days 1–3 were sacrificed by swift decapitation then the hearts were removed and minced immediately.…”

“…In addition, Trim27 plays some roles in diseases such as lung cancer, tuberculosis, hepatitis C virus [ 19 ], diabetes, Parkinson’s, and allergies [ 20 ]. Trim27 also mediated abnormal mesangial cell proliferation in the kidney of lupus [ 21 ]. Trim27 was reported to inhibit the kinase activity of PI3KC2β, resulting in reduced KCa3.1 channel activity and a decrease in Ca2+ influx and cytokine production stimulated by T-cell receptor (TCR) [ 22 ].…”

MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

“…For small interfering RNA (siRNA) treatment, the Akt-specific siRNA (GenBank accession number NM_009652.3) and the scrambled control siRNA oligonucleotides were obtained and AAV-siRNA/Akt (siAkt) and AAV-siRNA/control (siCON) were produced as previously [18,23]. Both kidneys of the mice were treated with siAkt or siCON at a dose of 1.6 × 10 11 viral genomes using orthotopic injection [24,25].…”

Tripartite Motif‐Containing 27 Attenuates Liver Ischemia/Reperfusion Injury by Suppressing Transforming Growth Factor β–Activated Kinase 1 (TAK1) by TAK1 Binding Protein 2/3 Degradation

“…(8) As a member of the TRIM family, which contains similar domains of a RING (really interesting new gene) finger, B-box zinc finger, and coiled-coil domain, TRIM27 was first reported as a fusion protein of the RET proto-oncogene in 1988. (9,10) TRIM27 has been shown to negatively regulate antiviral and inflammatory responses through inhibition NF-κB and interferon activation mediated by IκB kinase (IKK)α/β/ε. (11) Moreover, TRIM27 knockdown induced cell apoptosis in ovarian cancer cells by up-regulating phosphorylated p38 (p-p38).…”