Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat) with Diabetic Nephropathy

Abstract

Qufengtongluo (QFTL) decoction is an effective treatment for diabetic nephropathy (DN). However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-β, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-β mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-β was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-β.

Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression

“…Furthermore, our results revealed a significant upregulation of the PI3K/Akt/mTOR pathway in MTX-treated rats and this may be explained by what was reported about the capability TGF-β in activating the PI3K/Akt/mTOR pathway [37,38]. Several reports demonstrated the involvement of the PI3K/Akt signaling in the pathogenesis of chemotherapy induced-nephrotoxicity like doxorubicin [11], MTX [5], and cisplatin [39,40].…”

“…Controversial results were reported in the PI3K/Akt pathway in different experimental models of induced-kidney injury. Some researchers reported its activation in the injured kidney [37,38,39,41,42,43,44] while others reported its downregulation [5,45,46,47,48]. This may be explained by using different animal models, experimental conditions, duration, therapies, phosphorylation sites analyzed, and detection methods in addition to the early and late stages of renal diseases [11,49,50].…”

Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats

“…Our results showed that high-, medium- and low-dose Dex significantly inhibited β2-MG and α1-MG levels in rat urine, indicating that Dex prevented and delayed early renal dysfunction in DM rats. Masson staining highlights deposition of immune complexes on the glomerulus, basement membrane, mesangial matrix, and collagen fibers, and is crucial for assessment of renal fibrotic lesions [13]. Our results showed that Dex significantly inhibited deposition of fibrous material in rat kidney tissue.…”

Anhuienoside C Attenuates Podocyte Injury in Diabetic Nephropathy Rats

“…The PI3K/Akt signaling pathway and NF-κB also contribute to the regulation of podocyte function. For example, Akt kinase is activated by TGF-β in diabetic kidneys, 35 and the morphology and function of podocytes are maintained by nephrin, which involves PI3K. PI3K also controls the excretion of microalbuminuria in DN.…”