Tissue & cell · 2026
Influence of Vimentin and E-cadherin on the development of interstitial fibrosis in focal and segmental glomerulosclerosis - FSGS.
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Rocha Laura Penna, Urzêdo Monise Gini, Donzelli Nayne Isabelli Zugolaro, de Freitas Oliveira Bruna, Silva Crislaine Aparecida, Zaidan Bruna Cunha, Lira Fusco Régia Caroline Peixoto, Dos Reis Marlene Antônia, Machado Juliana Reis
Аннотация
INTRODUCTION: Podocytopathies, including Focal and Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD), are among the main causes of nephrotic syndrome, with FSGS being more associated with progression to renal fibrosis and chronic kidney disease. Epithelial-mesenchymal transition (EMT) is an important mechanism involved in renal fibrosis, in which epithelial cells acquire characteristics and functions of mesenchymal cells.
METHODS: Fifty-four renal biopsies were analyzed and divided between FSGS (n = 30) and MCD (n = 24). The control group was obtained from autopsy cases without renal alterations (n = 10). The immunostaining of E-cadherin, vimentin, and fibronectin was evaluated by immunohistochemistry, while interstitial fibrosis (IF) was analyzed using Picro Sirius staining. Epidemiological and clinical information of these patients was also evaluated. Statistical analysis was performed using GraphPad Prism.
RESULTS: FSGS presented more cases of advanced IF, greater immunostaining of vimentin and fibronectin, and lower immunostaining of E-cadherin compared to the control group. Additionally, IF correlated positively with vimentin and negatively with E-cadherin. A lower E-cadherin-to-vimentin ratio was strongly associated with higher interstitial fibrosis and a greater percentage of globally sclerosed glomeruli. Patients with nephrotic proteinuria showed a significantly lower E-cadherin-to-vimentin ratio compared with those without nephrotic proteinuria.
CONCLUSION: The lower the E-cadherin/vimentin ratio, the greater the degree of chronic renal damage, suggesting that partial EMT is associated with an increased risk of progression to ESRD. Moreover, partial EMT may be more present in FSGS, since vimentin and E-cadherin were the markers most associated with the development of fibrosis. The identification of these markers may assist in prognosis and in the development of antifibrotic therapies.
METHODS: Fifty-four renal biopsies were analyzed and divided between FSGS (n = 30) and MCD (n = 24). The control group was obtained from autopsy cases without renal alterations (n = 10). The immunostaining of E-cadherin, vimentin, and fibronectin was evaluated by immunohistochemistry, while interstitial fibrosis (IF) was analyzed using Picro Sirius staining. Epidemiological and clinical information of these patients was also evaluated. Statistical analysis was performed using GraphPad Prism.
RESULTS: FSGS presented more cases of advanced IF, greater immunostaining of vimentin and fibronectin, and lower immunostaining of E-cadherin compared to the control group. Additionally, IF correlated positively with vimentin and negatively with E-cadherin. A lower E-cadherin-to-vimentin ratio was strongly associated with higher interstitial fibrosis and a greater percentage of globally sclerosed glomeruli. Patients with nephrotic proteinuria showed a significantly lower E-cadherin-to-vimentin ratio compared with those without nephrotic proteinuria.
CONCLUSION: The lower the E-cadherin/vimentin ratio, the greater the degree of chronic renal damage, suggesting that partial EMT is associated with an increased risk of progression to ESRD. Moreover, partial EMT may be more present in FSGS, since vimentin and E-cadherin were the markers most associated with the development of fibrosis. The identification of these markers may assist in prognosis and in the development of antifibrotic therapies.