Premium
Role of melatonin receptor 1A and pituitary homeobox‐1 coexpression in protecting tubular epithelial cells in membranous nephropathy
Author(s) -
Huang YenSung,
Lu KuoCheng,
Chao TaiKuang,
Chen JinShuen,
Chen Ann,
Guo ChengYi,
Hsieh HsinYi,
Shih HsiuMing,
Sytwu HueyKang,
Wu ChiaChao
Publication year - 2018
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12482
Subject(s) - luzindole , medicine , endocrinology , downregulation and upregulation , creb , biology , receptor , melatonin receptor , melatonin , chemistry , transcription factor , biochemistry , gene
Membranous nephropathy ( MN ), a type of glomerular nephritis, is one of the most common causes of nephrotic syndrome in adults. Although it is known that melatonin plays a protective role in MN , the role of melatonin receptors in the pathophysiology of MN is unclear. Using an experimental MN model and clinical MN specimens, we studied melatonin receptor expression and found that melatonin receptor 1A ( MTNR 1A) expression was significantly downregulated in renal tubular epithelial cells. Molecular studies showed that the transcription factor pituitary homeobox‐1 ( PITX 1) promoted MTNR 1A expression via direct binding to its promoter. Treatment of a human tubular cell line with albumin to induce injury resulted in the stable reduction in MTNR 1A and PITX 1 expression. PITX 1 levels were significantly downregulated in tubular epithelial cells from mice MN kidneys and MN renal specimens. Knockdown of MTNR 1A, PITX 1, or cyclic adenosine monophosphate‐responsive element‐binding protein ( CREB ) decreased E‐cadherin ( CDH 1) expression, but upregulated Per2 and α‐smooth muscle actin (α SMA ) expression. Blockade of the MTNR 1A receptor with luzindole in MN mice further impaired renal function; this was accompanied by CDH 1 downregulation and Per2 and α SMA upregulation. Together, our results suggest that in injured tissue, decreased PITX 1 expression at the MTNR 1A promoter regions leads to decreased levels of MTNR 1A in renal tubular epithelial cells, which increases the future risk of MN .