1. The role of mammalian target of rapamycin pathway in the pathogenesis of pauci-immune glomerulonephritis
- Author
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Zeki Soypacaci, Ozlem Zekiye Cakmak, Ibrahim Ertekin, Onay Gercik, Servet Akar, Atilla Uzum, Rifki Ersoy, and Fulya Cakalagoglu
- Subjects
Male ,Pathology ,Biopsy ,mTOR protein ,Kidney Glomerulus ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Critical Care and Intensive Care Medicine ,Pathogenesis ,0302 clinical medicine ,Glomerulonephritis ,Transforming Growth Factor beta ,PTEN protein ,Crescentic glomerulonephritis ,TOR Serine-Threonine Kinases ,food and beverages ,General Medicine ,Pauci-immune glomerulonephritis ,Middle Aged ,Immunohistochemistry ,female genital diseases and pregnancy complications ,Nephrology ,Disease Progression ,Female ,medicine.symptom ,Immunosuppressive Agents ,Signal Transduction ,Adult ,medicine.medical_specialty ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Lesion ,03 medical and health sciences ,medicine ,Humans ,latency associated protein TGF B1 ,Aged ,Autoantibodies ,Retrospective Studies ,urogenital system ,business.industry ,MTOR Protein ,PTEN Phosphohydrolase ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Diseases of the genitourinary system. Urology ,PTEN Protein ,Pauci-immune ,Clinical Study ,pathology ,RC870-923 ,business - Abstract
Background: The characteristic lesion of pauci-immune glomerulonephritis is focal necrotizing and crescentic glomerulonephritis. The underlying mechanisms in the formation or progression of crescent formation need further investigations. Therefore, we aimed to evaluate the role of mammalian target of rapamycin (mTOR), which might be a potential therapeutic target, in kidney biopsies of patients with pauci-immune glomerulonephritis. Methods: The patients diagnosed as pauci-immune glomerulonephritis at an outpatient nephrology clinic were retrospectively reviewed and those patients who had a kidney biopsy before receiving an immunosuppressive treatment were included in the study. Kidney biopsy specimens were immunohistochemically stained with mTOR, antibodies of phosphatase and tensin homolog (PTEN) and transforming growth factor-β (TGF-β) and scored by an experienced renal pathologist. Results: In total, 54 patients with pauci-immune glomerulonephritis (28 [52%] female) were included. According to the histopathologic examination, 22% of our cases were classified as focal, 33% crescentic, 22% mixed, and 22% as sclerotic. The mTOR was expressed in substantial percentages of glomeruli of patients with pauci-immune glomerulonephritis. However, we observed PTEN expression in all samples and mTOR in all tubulointerstitial areas. mTOR expression was found to be related with the presence of crescentic and sclerotic changes observed in glomeruli and the degree of fibrosis in interstitial areas. Serum creatinine level or response to treatment was not found to be associated with mTOR pathway expression. Conclusion: Our results suggest that mTOR pathway may play role in the pathogenesis of pauci-immune glomerulonephritis, besides targeting this signaling may be an alternative option for those patients.
- Published
- 2019