التفاصيل البيبلوغرافية
| العنوان: |
Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment. |
| المؤلفون: |
Lee, Yashang, Blount, Katrina Lehmann, Dai, Feng, Thompson, Siobhan, Scher, Jonathan Kaufman, Bitterman, Sherrie, Droher, Madeline, Herzog, Erica L., Moeckel, Gilbert, Karihaloo, Anil, Dahl, Neera K. |
| المصدر: |
Clinical & Experimental Nephrology; Aug2018, Vol. 22 Issue 4, p906-916, 11p |
| مصطلحات موضوعية: |
POLYCYSTIC kidney disease treatment, SEMAPHORINS, T cells, PULMONARY fibrosis, CHRONIC kidney failure |
| مستخلص: |
Background: Semaphorin 7A (SEMA7A) is an immunomodulating protein implicated in lung and liver fibrosis. In autosomal-dominant polycystic kidney disease (ADPKD), the progressive expansion of renal cysts, inflammation, and subsequent renal fibrosis leads to end-stage renal disease (ESRD). SEMA7A may play a role in renal fibrosis and in ADPKD.Methods: We evaluated Sema7a in a mouse model of renal fibrosis and determined the expression of SEMA7A in human ADPKD kidney. We analyzed SEMA7A expression on peripheral blood mononuclear cells (PBMCs), including CD45+ (leukocyte), CD14+(monocyte), CD4+ (T lymphocytes) and CD4+Foxp3+CD25+ [regulatory T lymphocytes (Tregs)] from 90 ADPKD patients (11 tolvaptan treated and 79 tolvaptan naïve), and 21 healthy volunteers, using a Fluorescence-Activated Cell Sorting (FACS).Results: Sema7a is required for renal fibrosis. SEMA7A shows robust expression in ADPKD kidneys, localizing to cysts derived from distal tubules. SEMA7A is higher in circulating monocytes, but unchanged in CD4+ lymphocytes in ADPKD patients. The SEMA7A increase was detected early (stage 1 CKD) and seemed more prominent in patients with smaller kidneys (p = 0.09). Compared to tolvaptan-naïve ADPKD patients, those treated with tolvaptan showed reduced SEMA7A expression on monocytes, T lymphocytes, and Tregs, although the number of PBMCs was unchanged. After 1 month of tolvaptan treatment, SEMA7A expression on Tregs decreased.Conclusions: SEMA7A shows potential as both a therapeutic target in mammalian kidney fibrosis and as a marker of inflammation in ADPKD patients. SEMA7A expression was lower after tolvaptan treatment, which may reflect drug efficacy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
