Role of STAT3/mTOR pathway in chronic kidney injury

STAT3/mTOR pathway plays an important role in inflammation, cell growth, and proliferation. However, the role of STAT3/mTOR pathway in chronic kidney injury remains unclear. Folic acid was used to induce kidney injury C57BL/6 mouse model followed by analysis of serum creatinine, renal weight ratio changes, renal pathological changes and STAT3/mTOR pathway changes. Glomerular mesangial cells were divided into control group, model group, STAT3 inhibitor (S3I-201) group followed by analysis of cell proliferation by MTT assay, cell apoptosis by flow cytometry, formation of autophagosomes by electron microscopy, expression of STAT3/mTOR signaling proteins and autophagy proteins LC3II and p62 by Western blot, expression of E-cadherin and Vimentin by immunofluorescence. The serum creatinine and renal weight ratio was increased with obvious lesions and upregulated STAT3 and p-mTOR level. Compared with control group, the difference was statistically significant (P < 0.05). Folic acid-induced injury of mesangial cells showed inhibited cell proliferation, promoted apoptosis, increased LC3II expression, decreased p62 expression, increased autophagic vacuoles and expression of STAT3 and p-mTOR as well as decreased E-cadherin expression and increased Vimentin expression. The difference was statistically significant compared with control group (P < 0.05). All above changes were significantly reversed after treatment with STAT3 inhibitor S3I-201 (P < 0.05). Activated STAT3/mTOR pathway, enhanced autophagy, promoted apoptosis of mesangial cells and inhibited cell proliferation were found in mice with renal injury. Inhibition of STAT3/mTOR activation inhibits autophagy and cell apoptosis and promotes cell proliferation.