Genetic Deletion of the Lipid Raft Protein Caveolin-1 Leads to Worsening Renal Fibrosis (2018)

Type of publication:
Journal article

*Chand S, Hazeldine J, Smith S, Borrows R.

Journal of Clinical Nephrology and Renal Care 2018 Jun;4(1):037

Renal disease is a major global public health issue. Renal interstitial fibrosis is the characteristic histopathological finding in all progressive renal disease. Caveolin-1 is the essential structural protein for lipid rafts called caveolae that are ubiquitously distributed among fibroblasts, endothelial and epithelial cells. Caveolin-1 acts as an intracellular signalling pathway chaperone in fibrotic disease. Presently, caveolin-1 expression is associated with more severe renal disease in human and previous murine studies. In non-renal fibrosis, caveolin-1 protects against fibrosis. The purpose of this study was to investigate if caveolin-1 knockout led to an increased fibrotic phenotype using the unilateral ureteric obstruction model of renal fibrosis.
Using 2 time-points of the unilateral ureteric obstruction model, wild-type and caveolin-1 knockout mouse kidneys were analysed for caveolin-1 expression and markers of fibrosis using histology, Gomori staining, real-time quantified polymerase chain reaction, Western blotting and confocal microscopy.
Confocal microscopy shows caveolin-1 staining mainly in glomerulus, lining of tubules as well as the vasculature. There was increased caveolin-1 expression the longer the unilateral obstruction occurred as well as in the contralateral compensating non-obstructed kidney. Caveolin-1 knockout had less fibrosis at day 3 histologically but more at day 14 as compared to wild-type. There were significantly more F4/80 positive staining cells at day 3 and day 14 in the wild-type injured kidney as compared to the caveolin-1 knockout mouse.
Caveolin-1 knockout leads to a worse fibrosis upon unilateral ureteric obstruction. Caveolin-1 expression manipulation timing remains to be elucidated in reducing renal fibrosis.

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