Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Μπολέτης Ιωάννης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καβαντζάς Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βασιλόπουλος Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γακιοπούλου Χαρίκλεια, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Φούκας Περικλής, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρινάκη Σμαράγδη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Λιονάκη Σοφία, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Παθολογοανατομική μελέτη δεικτών εμπλεκόμενων στην παθογένεια της ιστικής βλάβης στις σπειραματονεφρίτιδες
Translated title:
Histopathological study of markers involved in the pathogenesis of glomerulonephritis
Summary:
Introduction: Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β1/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). Methods: We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semi-quantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. Results: TGF-β1 expression correlated positively with segmental glomerulosclerosis (p=0.025) and creatinine level at diagnosis (p=0.002), while pSmad3 expression with interstitial inflammation (p=0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (p=0.011), intense interstitial inflammation (p=0.029) and lower serum complement 3 (p=0.028) and complement 4 (p=0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (p=0.045) and in podocytes of non-proliferative GN (p=0.005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR= 6.078; 95%CI 1.168-31.627; p=0.032) was emerged as independent predictor for progression to CKD. Discussion/Conclusion: TGF-β1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.
Main subject category:
Health Sciences
Keywords:
Glomerulonephritis, Renal biopsy, pathogenesis, Transforming growth factor β (TGF-β), Smad proteins, Immunohistochemical study
Number of references:
271
