PMID- 26016809
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20210719
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 67
IP  - 9
DP  - 2015 Sep
TI  - The Role of MicroRNAs and Human Epidermal Growth Factor Receptor 2 in 
      Proliferative Lupus Nephritis.
PG  - 2415-26
LID - 10.1002/art.39219 [doi]
AB  - OBJECTIVE: To understand the roles of microRNAs (miRNAs) in proliferative lupus 
      nephritis (LN). METHODS: A high-throughput analysis of the miRNA pattern of the 
      kidneys of LN patients and controls was performed by molecular digital detection. 
      Urinary miRNAs were measured by quantitative reverse transcription-polymerase 
      chain reaction (qRT-PCR). Target gene expression in human mesangial cells was 
      evaluated by arrays and qRT-PCR. Human epidermal growth factor receptor 2 (HER-2) 
      was analyzed by immunohistochemistry in kidney samples from LN patients and in a 
      murine model of lupus. Urinary levels of HER-2, monocyte chemotactic protein 1 
      (MCP-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured by 
      enzyme-linked immunosorbent assay. RESULTS: Levels of the miRNAs miR-26a and 
      miR-30b were decreased in the kidneys and urine of LN patients. In vitro these 
      miRNAs controlled mesangial cell proliferation, and their expression was 
      regulated by HER-2. HER-2 was overexpressed in lupus-prone NZM2410 mice and in 
      the kidneys of patients with LN, but not in other mesangioproliferative 
      glomerulonephritides. HER-2 was found to be up-regulated by interferon-alpha and 
      interferon regulatory factor 1. Urinary HER-2 was increased in LN and reflected 
      disease activity, and its levels correlated with those of 2 other recognized LN 
      biomarkers, MCP-1 and VCAM-1. CONCLUSION: The kidney miRNA pattern is broadly 
      altered in LN, which contributes to uncontrolled cell proliferation. Levels of 
      the miRNAs miR-26a and miR-30b are decreased in the kidneys and urine of LN 
      patients, and they directly regulate the cell cycle in mesangial cells. The 
      levels of these miRNAs are controlled by HER-2, which is overexpressed in NZM2410 
      mice and in the kidneys and urine of LN patients. HER-2, miR-26a, and miR-30b are 
      thus potential LN biomarkers, and blocking HER-2 may be a promising new strategy 
      to decrease cell proliferation and damage in this disease.
CI  - (c) 2015, American College of Rheumatology.
FAU - Costa-Reis, Patricia
AU  - Costa-Reis P
AD  - The Children's Hospital of Philadelphia and University of Pennsylvania Perelman 
      School of Medicine, Philadelphia, and University of Lisbon, Lisbon, Portugal.
FAU - Russo, Pierre A
AU  - Russo PA
AD  - The Children's Hospital of Philadelphia and University of Pennsylvania Perelman 
      School of Medicine, Philadelphia.
FAU - Zhang, Zhe
AU  - Zhang Z
AD  - The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Colonna, Lucrezia
AU  - Colonna L
AD  - The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Maurer, Kelly
AU  - Maurer K
AD  - The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Gallucci, Stefania
AU  - Gallucci S
AD  - The Children's Hospital of Philadelphia and Temple University, Philadelphia, 
      Pennsylvania.
FAU - Schulz, Steffan W
AU  - Schulz SW
AD  - Hospital of the University of Pennsylvania, Philadelphia.
FAU - Kiani, Adnan N
AU  - Kiani AN
AD  - Johns Hopkins University School of Medicine, Baltimore, Maryland.
FAU - Petri, Michelle
AU  - Petri M
AD  - Johns Hopkins University School of Medicine, Baltimore, Maryland.
FAU - Sullivan, Kathleen E
AU  - Sullivan KE
AD  - The Children's Hospital of Philadelphia and University of Pennsylvania Perelman 
      School of Medicine, Philadelphia.
LA  - eng
GR  - R01 AR043727/AR/NIAMS NIH HHS/United States
GR  - R01 AR058547/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Chemokine CCL2)
RN  - 0 (MIRN26A microRNA, human)
RN  - 0 (MIRN30b microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - Chemokine CCL2/*urine
MH  - Child
MH  - Disease Models, Animal
MH  - Female
MH  - Glomerulonephritis, Membranoproliferative/genetics/metabolism
MH  - Humans
MH  - Kidney/*metabolism
MH  - Lupus Nephritis/*genetics
MH  - Male
MH  - Mesangial Cells/*metabolism
MH  - Mice
MH  - MicroRNAs/*metabolism/urine
MH  - Receptor, ErbB-2/*metabolism/urine
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Cell Adhesion Molecule-1/*urine
PMC - PMC7814461
MID - NIHMS1651974
EDAT- 2015/05/29 06:00
MHDA- 2015/11/17 06:00
PMCR- 2021/01/19
CRDT- 2015/05/29 06:00
PHST- 2014/06/27 00:00 [received]
PHST- 2015/05/21 00:00 [accepted]
PHST- 2015/05/29 06:00 [entrez]
PHST- 2015/05/29 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
PHST- 2021/01/19 00:00 [pmc-release]
AID - 10.1002/art.39219 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2015 Sep;67(9):2415-26. doi: 10.1002/art.39219.