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Chinese Journal of Clinicians(Electronic Edition) ›› 2021, Vol. 15 ›› Issue (09): 683-690. doi: 10.3877/cma.j.issn.1674-0785.2021.09.008

• Basic Science Research • Previous Articles     Next Articles

Mechanism of action of JAK2/STAT3 signaling pathway in podocyte injury in focal segmental glomerulosclerosis

Jiefeng Zou1, Yunpeng Xu1, Yanzi Zhang1, Xiaolu Sui1, Shuzhen Yuan1, Qicheng Zeng1, Lixiang Li1, Tingfei Xie1, Zibin Xu1, Jihong Chen1,()   

  1. 1. Department of Nephrology, Affiliated Bao'an Hospital of Shenzhen, The Second School of Clinical Medicine, Southern Medical University, Shenzhen 518000, China.
  • Received:2021-01-31 Online:2021-09-15 Published:2022-01-20
  • Contact: Jihong Chen

Abstract:

Objective

To establish a mouse model of adriamycin-induced focal segmental glomerulosclerosis and explore the mechanism of action of the JAK2/STAT3 signaling pathway in FSGS podocyte injury.

Methods

Eight-week-old male C57BL/6 mice were randomly divided into either FSGS group (n=20) or control group (n=20) randomly. The FSGS group was given a single tail vein injection of 25 mg/kg adriamycin, and the control group was given the same dose of PBS solution. Indexes including 24-h urinary protein, blood urea nitrogen (BUN), and serum creatinine (Scr) were measured. Renal histopathology was observed by HE staining. The glomerular basement membrane thickness and the morphology of podocytes were observed by transmission electron microscopy. Dual immunofluorescence staining for nephrin and podocin in podocytes were observed by laser confocal microscopy. Podocyte apoptosis was detected by TUNEL. The expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) mRNA was measured by real-time PCR. The expression of JAK2 and STAT3 proteins was measured by Western blot. The contents of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) were detected by enzyme linked immunosorbent assay (ELISA).

Results

Compared with the control group, 24-h urinary protein, BUN, and Scr were significantly increased in the FSGS group (P<0.01 for all). In the FSGS group, there was stromal proliferation in mesangial area, apoptosis and necrosis of renal tubular epithelial cells, moderately aggravated segments, compressed and narrowed capillary structure, and obvious proliferation of podocytes; electron microscopy showed that glomerular basement membrane was thickened and podocytes were fused; the expression of nephrin and podocin in podocytes was decreased, and the apoptosis of podocytes was increased. Compared with the control group, the expression of JAK2/STAT3 mRNA and proteins, as well as the contents of IL-6, MCP-1, α-SMA, and TGF-β1, was significantly elevated in the FSGS group (P<0.01 for all).

Conclusion

Adriamycin-induced FSGS mouse model is stable and reliable. The JAK2/STAT3 signaling pathway activation participates in the development of podocyte injury in FSGS by promoting downstream factor activation, oxidative stress, apoptosis and other pathways.

Key words: Focal segmental glomerulosclerosis, Podocytes, JAK2/STAT3 signaling pathway, Adriamycin

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