Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy |
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| Authors: | Keiko Tanaka Hitoshi Sugiyama Toshio Yamanari Koki Mise Hiroshi Morinaga Masashi Kitagawa Akifumi Onishi Ayu Ogawa‐Akiyama Katsuyuki Tanabe Jun Eguchi Yasukazu Ohmoto Kenichi Shikata Jun Wada |
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| Institution: | 1. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;2. Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;3. Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan;4. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan |
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| Abstract: | Aim Trefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN). Methods We investigated the renal mRNA expression of TFF3 by real‐time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively. Results The renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients. Conclusion Renal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients. |
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| Keywords: | fibrosis IGA nephropathy renal biopsy TFF3 tubular epithelium |
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