| BackgroundFSGS is a common pathological type of various renal diseases such as diabetic nephropathy,HIVAN,glomerulonephritis.Multiple signaling pathways,such as Notch、MAPK、PI3K/Akt、JAK/STAT,are activated during FSGS progression,inducing podocyte injury and glomerulosclerosis.Activation of the JAK/STAT signaling pathway mediates cell proliferation and growth,differentiation and migration,apoptosis,inflammatory response,immune regulation and other pathophysiological processes,causing podocyte injury and aggravating glomerulosclerosis and tubulointerstitial fibrosis.It is also widely involved in the development of FSGS,diabetic nephropathy,obstructive nephropathy,polycystic kidney and other renal diseases.The JAK2/STAT3 signaling pathway has become the focus of kidney disease research.In this study,FSGS mouse model was established by precise 5/6 nephrectomy.24-hour urinary protein,serum creatinine,blood urea nitrogen,renal histopathological changes,JAK2/STAT3 signal pathway target gene,protein,downstream inflammatory and fibrosis factors were observed to reveal the pathogenesis of JAK2/STAT3 signal pathway involved in the progression of FSGS.MethodsMale C57BL/6 mice were divided into two groups randomly,control group(n=30)and FSGS group(n=30).The control group was treated with sham operation and FSGS mouse model was established by precise 5/6 nephrectomy.The volume formula was used to calculate the required nephrectomy size,and the maximum length of left kidney was measured.According to the calculation results,the upper and lower poles of the left kidney were ligated at the corresponding position,2/3 left kidney was removed along the ligation position,followed by right kidney removed 1 week later.24h urinary protein,serum creatinine(Scr)and blood urea nitrogen(BUN)were measured by automatic biochemical analyzer.The renal histopathology was observed by HE staining.The target mRNA expressions in JAK2/STAT3 signaling pathway were detected by RTPCR.The target protein expressions in JAK2/STAT3 signaling pathway were detected by Western blotting.The levels of downstream factors were detected by ELISA.Results1.The levels of 24h urinary protein,Scr and BUN significantly increased in FSGS group(P<0.01).Renal histopathology in the FSGS group showed renal tubular epithelial cells apoptosis,necrosis,and Bowman’s capsule dilatation,compensatory glomerular hypertrophy and focal sclerosis,mesangial cells and mesangial matrix hyperplasia,accompanied by inflammatory cells infiltration.The FSGS mouse model was established by precise 5/6 nephrectomy.The mortality rate of model mice was 10.3%,and the success rate of modeling making was 89.7%.2.Compared with the control group,the mRNA and the protein expressions were elevated in the FSGS group,as well as the downstream inflammatory factors and fibrosis factors(IL-6,MCP-1,α-SMA,TGF-β1)in JAK2/STAT3 signaling pathway(P<0.01).ConclusionsFSGS mouse model was successfully established by precision 5/6 nephrectomy,which is better than the traditional model,presenting typical FSGS features.The mortality rate of model mice was low,and the success rate of modeling was high.JAK2/STAT3 signaling pathway activation is involved in the development of FSGS by promoting inflammation,renal fibrosis,and other pathways. |
