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A molecular morphometric approach to diabetic kidney disease can link structure to function and outcome.

Abstract：

:Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes. Tissue obtained from protocol kidney biopsies underwent genome-wide compartment-specific gene expression profiling and quantitative morphometric analysis. The ultrastructural lesion most strongly associated with transcriptional regulation was cortical interstitial fractional volume (VvInt), an index of tubule-interstitial damage. Transcriptional co-expression network analysis identified 1843 transcripts that correlated significantly with VvInt. These transcripts were enriched for pathways associated with mitochondrial dysfunction, inflammation, migratory mechanisms, and tubular metabolic functions. Pathway network analysis identified IL-1β as a key upstream regulator of the inflammatory response and five transcription factors cooperating with p53 to regulate metabolic functions. VvInt-associated transcripts showed significant correlation with the urine albumin to creatinine ratio and measured glomerular filtration rate 10 years after biopsy, establishing a link between the early molecular events and long-term disease progression. Thus, molecular mechanisms active early in diabetic kidney disease were revealed by correlating intrarenal transcripts with quantitative morphometry and long-term outcomes. This provides a starting point for identification of urgently needed therapeutic targets and non-invasive biomarkers of early diabetic kidney disease.

journal_name

Kidney Int

journal_title

Kidney international

authors

Nair V,Komorowsky CV,Weil EJ,Yee B,Hodgin J,Harder JL,Godfrey B,Ju W,Boustany-Kari CM,Schwarz M,Lemley KV,Nelson PJ,Nelson RG,Kretzler M

doi

10.1016/j.kint.2017.08.013

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

439-449

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(17)30610-5

journal_volume

93

pub_type

杂志文章

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