MK-2206 Alleviates Renal Fibrosis by Suppressing the Akt/mTOR Signaling Pathway In Vivo and In Vitro

• DOI: 10.3390/cells11213505
• Publication Date: 2022-11-07T07:43:51Z
• Authors: Meiling Chen; Yihang Yu; Tao Mi; Qitong Guo; Bin Xiang; Xiaomao Tian; Liming Jin; Chunlan Long; Lianju Shen; Xing Liu; Jianbo Pan; Yuanyuan Zhang; Tao Xu; Deying Zhang; Guanghui Wei
• Keywords: 0303 health sciences; Akt/mTOR signaling pathway; QH573-671; TOR Serine-Threonine Kinases; renal fibrosis; Fibrosis; chronic kidney diseases; Article; 3. Good health; Transforming Growth Factor beta1; Mice; 03 medical and health sciences; chronic kidney diseases; renal fibrosis; MK-2206; Akt/mTOR signaling pathway; MK-2206; Humans; Animals; Kidney Diseases; Cytology; Proto-Oncogene Proteins c-akt; Signal Transduction; Ureteral Obstruction

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage disease. However, there are still no effective treatments reverse fibrosis. This study aimed explore the potential mechanism targeted drug for Here, unilateral ureteral obstruction (UUO)-treated mice TGF-β1-treated human tubular epithelial cell line (HK-2 cells) were used as models Based on changes mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted alleviate through bioinformatics. We dissolved with MK-2206 gastric gavage cultured TGF-β-induced HK-2 cells MK-2206. Histopathological examinations performed after intervention, degree fibrosis, well expression Akt/mTOR pathway-related proteins, evaluated immunohistochemical staining, immunofluorescence Western blot. The results showed that significantly improved structure kidney. Furthermore, intervention effectively inhibited UUO- TGF-β1-induced epithelial-mesenchymal transition, fibroblast activation, extracellular matrix deposition. Mechanistically, treatment attenuated activation signaling pathway. Taken together, our revealed first time promising improvement