Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway

Abstract

Background Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown. Methods An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats. Results The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats. Conclusions SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.

Long non-coding RNA TUG1 knockdown promotes autophagy and improves acute renal injury in ischemia-reperfusion-treated rats by binding to microRNA-29 to silence PTEN

“…Then, we also predicted that there are multiple target genes of miR-29a, including PTEN. At the same time, PTEN can affect the process of AKI-induced by I/R [ 26 – 28 ]. The dual-luciferase reporter gene assay further verified the binding relationship between TUG1 and miR-29, and between miR-29 and PTEN (Fig.…”

“…The directing targeting relationship between miR-29a and PTEN was reported previously in osteosarcoma cells [ 41 ]. miR-29a mimic protects against cell injury and mitochondrial dysfunction after ischemia-like stresses in vitro , and increasing miR-29a expression might be a novel option for protection against I/R injury [ 26 ]. Briefly, TUG1 could competitively bind to miR-29 to promote PTEN in I/R injury.…”

Analysis of microRNA Expression after Glutamine Intervention in Acute Renal Ischemia-Reperfusion Injury

“…miR-205 was significantly downexpressed in AKI patients and was found to be negatively correlated with SCr and BUN and was an independent risk factor for the prognosis of AKI patients [ 21 ]. miR-205 is considered a target for the treatment of oxidative stress- and autophagy-related pathological processes during AKI [ 22 , 23 ]. This implies that GLN may utilize miR-205 to regulate oxidative damage in AKI.…”

The HDAC2/SP1/miR-205 feedback loop contributes to tubular epithelial cell extracellular matrix production in diabetic kidney disease

“…regulates high glucose-induced mesangial cell ECM production by interacting with circLRP6 [46]. In addition, miR-205 exerts its protective effect by inhibiting the expression of PTEN [47,48], which may suppress the Smad3 pathway [49]. However, the precise role of miR-205 in DKD is largely unknown.…”