TSPAN1 silencing protects against cerulein‐induced pancreatic acinar cell injury via targeting AGR2

Abstract

Acute pancreatitis (AP) is an inflammatory gastrointestinal disorder affecting the pancreas. Previous study reported that tetraspanin 1 (TSPAN1) expression was significantly upregulated in the pancreas of AP patients. However, the underlying molecular mechanism of TSPAN1 in the pathogenesis of AP remains unclear. Thus, the aim of the present study was to investigate the potential role of TSPAN1 in development of AP. RT‐qPCR was carried out to quantify the relative mRNA levels of TSPAN1 and anterior gradient‐2 (AGR2). The CCK‐8 assay was used to detect the cell viability. The TUNEL assay was performed to visualize the apoptotic cells. Western blot was performed to determine the expressions of proteins related to endoplasmic reticulum (ER) stress and apoptosis. ELISA kits were adopted to detect the concentration of inflammatory cytokines including TNF‐α and IL‐6. Finally, immunoprecipitation (IP) was used to verify the interaction between TSPAN1 and AGR2. TSPAN1 was upregulated in serum of AP patients and AP cell models. TSPAN1 silencing promoted the cell proliferation and inhibited inflammatory response in cerulein‐induced AR42J cells. Moreover, TSPAN1 induced endoplasmic reticulum stress by binding AGR2. Interestingly, the overexpression of AGR2 abolished the effects of TSPAN1 silencing on cell proliferation and inflammatory response in cerulein‐induced AR42J cells. In summary, TSPAN1 silencing protects against cerulein‐induced pancreatic acinar cell injury through inhibiting ER stress‐mediated by AGR2. Hence, TSPAN1 may serve as a promising therapeutic target for AP treatment.

Single-cell RNA sequencing reveals the transcriptomic landscape of kidneys in patients with ischemic acute kidney injury

“…As shown in Figure 2 B, EC of ischemic AKI had elevated expression of IL -32 , which has pro-inflammatory properties and can trigger endoplasmic reticulum stress. [ 33 ] TSPAN1, promoting endoplasmic reticulum stress and apoptosis, [ 34 ] was upregulated in EC with ischemic AKI. EC had upregulated genes including cell adhesion molecules SPP1 , interferon-induced factor ( IFI6 ), apoptosis and lipid metabolism regulator ( PLIN2 ), and chemoattractant ( CXCL14 ).…”