Expression of caspase-3 and TGF- β1 in Fabry disease biopsies: Correlation with clinical parameters

BONDAR, CONSTANZA; MUCCI, J.M.; CRIVARO, ANDREA; VAENA E; ORMAZABAL, MAXIMILIANO; ROZENFELD, P.

Simposio; 19th WORLD Symposium Lysosomal Disease Network; 2023

Pathogenic mechanisms leading to Fabry nephropathy are not fully described. Lysosomal Gb3 deposition occurs followed by complex pathological pathways resulting in renal sclerosis/fibrosis. TGF-β1 is an important cytokine involved in fibrosis and apoptosis. Our previous results showed TGF-β1 and caspase-3 expression by tubular epithelial cells in biopsies from Fabry patients. The aim of this work was to quantify TGF-β1 and active caspase-3 expression by tubular cells in kidney biopsies from Fabry naïve patients and non-Fabry individuals, and to analyze possible correlations among these markers and clinical or histopathological parameters. To this end, 15 renal biopsies from naïve Fabry patients and 5 from non-Fabry individuals were included. Immunofluorescence staining for TGF-β1 and active-caspase-3 was performed. Fluorescence intensities were quantified using Image-J-software. These markers were compared among patients according to sex, age, classical or late onset Fabry disease, interstitial fibrosis and infiltration scores, proteinuria and glomerular filtration rate (GFR). Our results showed that TGF-β1 tubular expression was increased in the classic form compared to late onset group. Levels were independent from age or sex. Active-caspase-3 expression presented a similar tendency. There was no correlation between TGF-β1 and active-caspase-3 levels. Caspase-3 was elevated in patients presenting inflammatory infiltration. This marker also showed to correlate with proteinuria and GFR. No correlations were observed for TGF-β1 and histological/clinical parameters. In conclusion, TGF-β1 is highly expressed by tubular cells in kidney biopsies from Fabry naïve patients. TGF-β1 expression is higher in the classic form of the disease showing that this cytokine plays a key role in the pathogenesis. However, it showed no correlation with active-caspase-3. The apoptotic marker showed to correlate with proteinuria (positively) and GFR (negatively), suggesting that tubular cell death is a clear component of Fabry nephropathy, and it could be secondary to the increment in proteinuria levels.