Lumican overexpression exacerbates lipopolysaccharide-induced renal injury in mice

Abstract

The present study aimed to investigate the role of lumican in mice with endotoxin-induced acute renal failure (ARF). Lumican transgenic mice and wild-type mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to establish a model of ARF. The mice were sacrificed at 24 h and the blood and renal tissue samples were collected. The value of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to determine renal function. An ELISA was used to determined the concentrations of renal cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, IL-4 and IL-10. The protein expression levels of Toll-like receptor (TLR4) and nuclear factor (NF)κB in renal tissues were assessed using western blot analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was performed to monitor apoptosis of renal tissue. Light microscopy and electron microscopy were used to observe structural changes in the renal tissues. Following the administration of LPS, the SCr and BUN values of mice in the lumican transgenic group were higher compared with those in the control group. The expression levels of renal TLR4, NFκB, TNFα, IL-6, IL-4 and IL-10 were upregulated in the lumican transgenic mice compared with those in the wild-type control group. Apoptosis was detected predominantly on the renal tubule. There was a significant difference in the optical density of apoptotic bodies between the control mice and the lumican transgenic mice. Light and electron microscopy demonstrated more severe renal tissue injury in the lumican transgenic mice compared with that in the control mice. In conclusion, LPS may cause excessive apoptosis in the renal tubular cells via the TLR4 signal transduction pathway, a decrease in the number of renal tubular cells and ARF. Lumican may be important in mice with LPS-induced ARF.

Anti-apoptosis mechanism of triptolide based on network pharmacology in focal segmental glomerulosclerosis rats

“…However, IL4 may also be involved in the disease as a pro-inflammatory factor [21]. The expression level of IL4 is high in kidney tissue with acute kidney injury [22]. Therefore, the effect of IL4 on FSGS should be more extensively investigated.…”

Lumican is upregulated in osteoarthritis and contributes to TLR4-induced pro-inflammatory activation of cartilage degradation and macrophage polarization

“…Lumican (LUM) is a member of the SLRP family best known for its interaction with fibrillar collagens 23 and has recently emerged as a participant in hostepathogen interactions. LUM is known to interact with TLR4-ligand LPS, and LUM KO mice are hyporesponsive to LPS-induced septic shock 24,25 . Strikingly, LUM expression is significantly fragmented and reduced in OA cartilage (with fragmentation accounting for less than 50% of total protein) but is also upregulated in serum and SF of OA patients 21,22 .…”

Small Leucine-Rich Proteoglycans in Renal Inflammation: Two Sides of the Coin

“…62 LPS treatment of lumican-overexpressing mice led to enhanced production of TNF-α, IL-6, IL-4, and IL-10 in renal tissue compared with wild-type animals, which was associated with an acute decline of renal function. 62 However, it is still necessary to understand whether the soluble or sequestered or both forms of lumican are responsible for these effects. Asporin (class I SLRP) and fibromodulin (class II SLRP) 18 appear to display anti-inflammatory effects as described in the chapter below.…”

“…47 Only recently, lumican has been associated with renal disease. 62 LPS treatment of lumican-overexpressing mice led to enhanced production of TNF-α, IL-6, IL-4, and IL-10 in renal tissue compared with wild-type animals, which was associated with an acute decline of renal function. 62 However, it is still necessary to understand whether the soluble or sequestered or both forms of lumican are responsible for these effects.…”