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Abstract: PO1001

MMP-7 Affects Peritoneal Ultrafiltration Associated with Elevated Aquaporin-1 Expression via MAPK/ERK Pathway in Peritoneal Mesothelial Cells

Session Information

  • Peritoneal Dialysis
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 702 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Yin, Yue, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
  • Zhang, Fen, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
  • Xiao, Zhiwen, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
  • Zuo, Daming, Southern Medical University, Guangzhou, Guangdong, China
  • Ai, Jun, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
Background

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long-term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. Aquaporin-1 (AQP-1), one of the water-specific channel proteins distributed in the endothelium lining the peritoneal capillaries, facilitates the osmotic transport of water across the capillary endothelium, thereby playing an essential role in ultrafiltration during PD.

Methods

Human peritoneal mesothelial cell (HPMCs)line (HMrSV5) strain was continuously cultured in vitro and stimulated with MMP-7. The concentration gradient and time gradient stimulated were set up respectively. HMrSV5 cells were incubated with the suggested volume of lenti-virus negative and lenti-virus MMP-7. Western Blot, RNA isolation, real time PCR and immunofluorescence assay were used to detect the expression of MMP-7, AQP-1 and mitogen-activated protein kinases (MAPKs) phosphorylation in HMrSV5 cells, to verify that MMP-7 affects peritoneal ultrafiltration associated with elevated aquaporin-1 expression via MAPK/ERK pathway in peritoneal mesothelial cells.

Results

We showed that dialysate MMP-7 levels markedly increased in the patients with PD, and the elevated MMP-7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP-7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP-7 activated mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin-1 (AQP-1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP-7-mediating AQP-1 upregulation and cellular homeostasis.

Conclusion

In summary, all the findings indicate that MMP-7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP-7 might be a noninvasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.

Funding

  • Clinical Revenue Support