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Abstract: PO0932

Transgenic Mechano-Growth Factor Overexpression in Mice Induces Glomerular PKCα and Type I Collagen with Glomerulosclerosis

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Gao, Yongxin, University of Florida College of Medicine - Jacksonville, Jacksonville, Florida, United States
  • Hasan, Irtiza, University of Florida College of Medicine - Jacksonville, Jacksonville, Florida, United States
  • Rivera, Zaiyara Adorno, University of Florida College of Medicine - Jacksonville, Jacksonville, Florida, United States
  • Li, Hongwei, Southern Medical University, Guangzhou, Guangdong, China
  • Heilig, Charles W., University of Florida College of Medicine - Jacksonville, Jacksonville, Florida, United States
Background

Mechano-Growth Factor (MGF), a normally expressed component of several positive feedback loops in the renal glomerular mesangial cells (MC), was implicated by us in the control of glomerulosclerosis. Transgenic mice overexpressing MGF (LK440-mMGF) were produced to determine the role of MGF in glomerulosclerosis (GS).

Methods

Our previous studies demonstrated that MGF was induced in the glomeruli of diabetic mice with subsequent induction of several factors responsible for diabetic GS. In the current study, immunohistochemistry using specific antibodies was performed to compare the expression of select glomerular proteins involved in GS, in MGF–overexpressing transgenic mice (MGF Tg) vs. non-transgenic control mice (NT). DAB staining with 0-4+ scoring in glomeruli was performed, and p < 0.05 between groups was considered significant. PAS staining was performed to assess development of overall GS. The effects of transgenic MGF overexpression on mouse body weights and kidney weights was also assessed.

Results

A 2.5-fold higher expression of MGF was found in glomeruli of MGF Tg as compared to NT mice. This resulted in 2.1-fold increased expression of active PKC α, a potential mediator of the 2.2-fold increased GLUT1 expression observed. These changes appeared to drive the 2.2-fold increased Collagen Type I (Col-I) in glomeruli. All these prosclerotic factors likely contributed to the resultant GS, evidenced by 2.2-fold increased PAS positive material in MGF Tg glomeruli. All the above results were found to be significant with a P value <0.0001. Adult body weight in MGF Tg tended to be 8% higher in both males and females (NS). Mean kidney weights were 14% larger in MGF Tg vs same gender NT mice (NS).

Conclusion

1. MGF Tg displayed increased glomerular PKC α activation, Col-I protein, and PAS-positive extracellular matrix similar to diabetic GS with increased MGF. 2. Future studies of glomerular MGF inhibition in diabetic mice may help define the potential value of this maneuver in blocking GS.

Funding

  • Private Foundation Support