Abstract: PO0199
STC1 Prevents Lipopolysaccharide-Induced AKI via TGF-β
Session Information
- AKI Mechanisms - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Tan, Li, Sichuan University West China Hospital, Chengdu, Sichuan, China
- Qin, Wei, Sichuan University West China Hospital, Chengdu, Sichuan, China
- Tang, Yi, Sichuan University West China Hospital, Chengdu, Sichuan, China
Background
Lipopolysaccharide (LPS)-induced Epithelial injury plays a critical role in the pathogenesis of acute kidney injury (AKI). Stanniocalcin-1 (STC1), a pleiotropic glycoprotein, has been reported to protect ischemic renal injury by reducing redox oxygen species, modulating inflammatory release, and inhibiting cell apoptosis. However, regulators of STC1 expression as well as its physiologic function in kidneys were unknown. We sought to elucidate the relationship between TGF β and STC1 in LPS-induced kidney injury in vitro and in vivo and to define the functional role of STC1 expression in renal tubular epithelium.
Methods
C57BL/6 J mice, STC1-/- (C57BL/6 J background) mice were randomly divided into blank control group, experimental control group. A mouse model of AKI was established. Primary mouse renal tubular epithelial cells isolated from wide type mice and STC 1-/- mice were cultured. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, and measure the expression of signal pathway proteins and downstream inflammatory factors.
Results
LPS caused elevation of SCr, BUN level, morphological injury and tubular apoptosis, enhanced NLRP3 and Col 1 expression, and increased expression of TGF β and STC 1 (P<0.05).
Conclusion
Our study reveals a novel TGF β-STC1 pathway that has homeostatic as well as LPS-induced cytoprotective functions in renal tubular epithelium. STC 1 has protective effects on LPS-induced acute renal tubular injury in mice, possibly by targeting TGF β, enhencing TLR4 expression, regulating the TGF β/STC1 signaling pathway, and inhibiting the expression of downstream inflammatory factors.
Funding
- Government Support - Non-U.S.