Downregulation of miR‐29b‐3p aggravates podocyte injury by targeting HDAC4 in LPS‐induced acute kidney injury

Abstract

Sepsis is a severe organ dysfunction disease, usually accompanied by acute kidney injury (AKI). miR-29b-3p was inhibited in sepsis-induced AKI, while its role in AKI was unclear. Therefore, this study determined the role of miR-29b-3p in sepsisinduced AKI, and investigated its underlying mechanism. In this study, the AKI model was established through injecting with lipopolysaccharides (LPS) intraperitoneally. In LPS challenged mice, serum blood urea nitrogen and creatinine were increased, and renal tissues pathological damage was induced. Besides, miR-29b-3p was declined in LPS-induced AKI mice and podocytes. In addition, HDAC4 was elevated in LPStreated podocytes. Furthermore, upregulated miR-29b-3p attenuated LPS-induced mice podocyte injury, and HDAC4 was identified as a direct target of miR-29b-3p.Moreover, overexpression of miR-29b-3p attenuated LPS-induced AKI in mice. In conclusion, miR-29b-3p was inhibited in LPS-induced AKI. Downregulation of miR-29b-3p aggravated podocyte injury through targeting HDAC4 in LPS-induced AKI. miR-29b-3p may act as a valuable target for AKI therapy.

Revealing potential diagnostic gene biomarkers of septic shock based on machine learning analysis

“…Previous studies have found that the expression of UPP1 is increased in the brain of sepsis rats [ 49 ]. HDAC4 (histone deacetylase 4) plays an important regulatory role in sepsis and may be an effective target for sepsis treatment [ 50 , 51 ]. The expression level of NARF (nuclear prelamin A recognition factor) in multiple sclerosis (a chronic neuroinflammatory disease) was increased [ 52 ].…”

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats

“…To our knowledge, there are no data on the effect of sepsis on HDAC4 expression in skeletal muscle. However, LPS upregulates HDAC4 in mice podocyte cells MPC5 [ 59 ], and these authors concluded that HDAC4 mediates LPS-induced acute renal injury and podocyte injury. Furthermore, TMP195, an HDAC4 inhibitor, attenuates endotoxin-induced acute renal injury [ 60 ].…”

Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy

“…Previous researches confirmed that the LPS induces a significantly decreased expression of miR-29b in various cells. 36 – 38 For instance, study showed that compared to healthy individuals, miR-29b expression was reduced in the plasma of sepsis patients. LPS induced decrease expression of miR-29b in cardiomyocytes, and overexpression of miR-29b significantly alleviated the inflammatory in cardiomyocytes.…”