Glucose induces clonal selection and reversible dinucleotide repeat expansion in mesangial cells isolated from glomerulosclerosis-prone mice

Alessia Fornoni, Oliver Lenz, Liliane J. Striker, Gary E. Striker

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Clonal selection has been proposed as a pathogenetic mechanism in various chronic diseases, such as scleroderma, hypertension, pulmonary fibrosis, interstitial fibrosis of the kidney, atherosclerosis, and uterine leiomyomatosis. We previously found that mesangial cells from ROP mice prone to develop glomerulosclerosis changed their phenotype in response to high glucose concentrations. Here, we investigate whether clonal selection might contribute to this phenotype change. We found that in ROP mice at least two distinct mesangial cell clones exist. They are characterized by a different length of the d(CA) repeat in the MMP-9 promoter and exhibit a significantly different gene expression profile. Exposure of ROP mesangial cells to 25 mmol/l glucose for 35 days induces both clonal selection and reversible dinucleotide repeat expansion. None of these findings were present in mesangial cells isolated from C57BL/6 mice, which are not sclerosis-prone. We conclude that mesangial cell michrochimerism may be a marker for the susceptibility to glomerulosclerosis, that dinucleotide repeat expansion may be a novel mechanism for glucose-induced changes in gene expression, and that clonal selection may partially explain the change in mesangial cell phenotype in diabetes.

Original languageEnglish
Pages (from-to)2594-2602
Number of pages9
JournalDiabetes
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2003

Fingerprint

Dinucleotide Repeats
Mesangial Cells
Glucose
Phenotype
Leiomyomatosis
Pulmonary Fibrosis
Sclerosis
Matrix Metalloproteinases
Inbred C57BL Mouse
Transcriptome
Atherosclerosis
Fibrosis
Chronic Disease
Clone Cells
Hypertension
Kidney
Gene Expression
ROP

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucose induces clonal selection and reversible dinucleotide repeat expansion in mesangial cells isolated from glomerulosclerosis-prone mice. / Fornoni, Alessia; Lenz, Oliver; Striker, Liliane J.; Striker, Gary E.

In: Diabetes, Vol. 52, No. 10, 01.10.2003, p. 2594-2602.

Research output: Contribution to journalArticle

@article{73f04631ac1d40bca64f123d6645bafd,
title = "Glucose induces clonal selection and reversible dinucleotide repeat expansion in mesangial cells isolated from glomerulosclerosis-prone mice",
abstract = "Clonal selection has been proposed as a pathogenetic mechanism in various chronic diseases, such as scleroderma, hypertension, pulmonary fibrosis, interstitial fibrosis of the kidney, atherosclerosis, and uterine leiomyomatosis. We previously found that mesangial cells from ROP mice prone to develop glomerulosclerosis changed their phenotype in response to high glucose concentrations. Here, we investigate whether clonal selection might contribute to this phenotype change. We found that in ROP mice at least two distinct mesangial cell clones exist. They are characterized by a different length of the d(CA) repeat in the MMP-9 promoter and exhibit a significantly different gene expression profile. Exposure of ROP mesangial cells to 25 mmol/l glucose for 35 days induces both clonal selection and reversible dinucleotide repeat expansion. None of these findings were present in mesangial cells isolated from C57BL/6 mice, which are not sclerosis-prone. We conclude that mesangial cell michrochimerism may be a marker for the susceptibility to glomerulosclerosis, that dinucleotide repeat expansion may be a novel mechanism for glucose-induced changes in gene expression, and that clonal selection may partially explain the change in mesangial cell phenotype in diabetes.",
author = "Alessia Fornoni and Oliver Lenz and Striker, {Liliane J.} and Striker, {Gary E.}",
year = "2003",
month = "10",
day = "1",
doi = "10.2337/diabetes.52.10.2594",
language = "English",
volume = "52",
pages = "2594--2602",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "10",

}

TY - JOUR

T1 - Glucose induces clonal selection and reversible dinucleotide repeat expansion in mesangial cells isolated from glomerulosclerosis-prone mice

AU - Fornoni, Alessia

AU - Lenz, Oliver

AU - Striker, Liliane J.

AU - Striker, Gary E.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Clonal selection has been proposed as a pathogenetic mechanism in various chronic diseases, such as scleroderma, hypertension, pulmonary fibrosis, interstitial fibrosis of the kidney, atherosclerosis, and uterine leiomyomatosis. We previously found that mesangial cells from ROP mice prone to develop glomerulosclerosis changed their phenotype in response to high glucose concentrations. Here, we investigate whether clonal selection might contribute to this phenotype change. We found that in ROP mice at least two distinct mesangial cell clones exist. They are characterized by a different length of the d(CA) repeat in the MMP-9 promoter and exhibit a significantly different gene expression profile. Exposure of ROP mesangial cells to 25 mmol/l glucose for 35 days induces both clonal selection and reversible dinucleotide repeat expansion. None of these findings were present in mesangial cells isolated from C57BL/6 mice, which are not sclerosis-prone. We conclude that mesangial cell michrochimerism may be a marker for the susceptibility to glomerulosclerosis, that dinucleotide repeat expansion may be a novel mechanism for glucose-induced changes in gene expression, and that clonal selection may partially explain the change in mesangial cell phenotype in diabetes.

AB - Clonal selection has been proposed as a pathogenetic mechanism in various chronic diseases, such as scleroderma, hypertension, pulmonary fibrosis, interstitial fibrosis of the kidney, atherosclerosis, and uterine leiomyomatosis. We previously found that mesangial cells from ROP mice prone to develop glomerulosclerosis changed their phenotype in response to high glucose concentrations. Here, we investigate whether clonal selection might contribute to this phenotype change. We found that in ROP mice at least two distinct mesangial cell clones exist. They are characterized by a different length of the d(CA) repeat in the MMP-9 promoter and exhibit a significantly different gene expression profile. Exposure of ROP mesangial cells to 25 mmol/l glucose for 35 days induces both clonal selection and reversible dinucleotide repeat expansion. None of these findings were present in mesangial cells isolated from C57BL/6 mice, which are not sclerosis-prone. We conclude that mesangial cell michrochimerism may be a marker for the susceptibility to glomerulosclerosis, that dinucleotide repeat expansion may be a novel mechanism for glucose-induced changes in gene expression, and that clonal selection may partially explain the change in mesangial cell phenotype in diabetes.

UR - http://www.scopus.com/inward/record.url?scp=0141643283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141643283&partnerID=8YFLogxK

U2 - 10.2337/diabetes.52.10.2594

DO - 10.2337/diabetes.52.10.2594

M3 - Article

C2 - 14514645

AN - SCOPUS:0141643283

VL - 52

SP - 2594

EP - 2602

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -