Albumin activated the canonical NF-kB pathway as demonstrated by the increased nuclear translocation of the NF-kB p65 and p50 subunits and the transcriptional factors activity. These events of canonical NF-kB activation were partially suppressed by BMP-7. Albumin induced apoptosis in PTEC as evidenced by the up-regulated apoptotic index from the TUNEL assay and the increased caspase-8 activity. Interestingly, addition of BMP-7 further exaggerated these apoptotic events in PTEC overloaded with albumin. Conclusion: Our results demonstrated that BMP7 exaggerated the apoptotic events induced
by albumin in cultured PTEC. This amplification of the albumin-induced apoptosis was associated with the reduction of TNF-α synthesis and canonical NF-kB pathway activation. This study is supported by a General Research Fund of the Research Grants Council (#HKU 7770/09M) of Hong Kong and Matching Grant CYC202 from The University of Hong Kong. KODA RYO1,
YOSHINO ATSUNORI1, IMANISHI YUJI1, KAWAMOTO SHINYA1, UEDA YOSHIHIKO2, YAOITA EISHIN3, KAZAMA JUNICHIRO JAMES4, NARITA ICHIEI4, TAKEDA TETSURO1 1Department of Nephrology, Dokkyo Medical University Koshigaya Hospital; 2Department of Pathology, Dokkyo Medical University Koshigaya Hospital, Japan; 3Department of Structural Pathology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Japan; 4Division of Clinical Nephrology and Dorsomorphin chemical structure Rheumatology, Niigata University Graduate School of Medical and Dental Science, Japan Introduction: The origin of crescent forming cells in human glomerulonephritis
(GN) remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowman’s capsule G protein-coupled receptor kinase (PECs) were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. Methods: We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Co-localization of claudin-1 with intracellular tight junction protein ZO-1 was evaluated by immunofluorescence double staining. Expression of occludin, another fundamental intercellular tight junction protein, was also evaluated in crescentic lesion in human glomerulonephritis. Results: Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extra-junctional localization of claudin-1. Co-localization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Conclusion: Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1.