RGD Reference Report - Identification of periostin as a critical marker of progression/reversal of hypertensive nephropathy. - Rat Genome Database

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Identification of periostin as a critical marker of progression/reversal of hypertensive nephropathy.

Authors: Guerrot, D  Dussaule, JC  Mael-Ainin, M  Xu-Dubois, YC  Rondeau, E  Chatziantoniou, C  Placier, S 
Citation: Guerrot D, etal., PLoS One. 2012;7(3):e31974. doi: 10.1371/journal.pone.0031974. Epub 2012 Mar 5.
RGD ID: 10041032
Pubmed: PMID:22403621   (View Abstract at PubMed)
PMCID: PMC3293874   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0031974   (Journal Full-text)

Progression of chronic kidney disease (CKD) is a major health issue due to persistent accumulation of extracellular matrix in the injured kidney. However, our current understanding of fibrosis is limited, therapeutic options are lacking, and progressive degradation of renal function prevails in CKD patients. Uncovering novel therapeutic targets is therefore necessary.We have previously demonstrated reversal of renal fibrosis with losartan in experimental hypertensive nephropathy. Reversal was achieved provided that the drug was administered before late stages of nephropathy, thereby determining a non-return point of CKD progression. In the present study, to identify factors critically involved in the progression of renal fibrosis, we introduced losartan at the non-return point in L-NAME treated Sprague Dawley rats. Our results showed either reversal or progression of renal disease with losartan, defining 2 groups according to the opposite evolution of renal function. We took advantage of these experimental conditions to perform a transcriptomic screening to identify novel factors potentially implicated in the mechanisms of CKD progression. A secondary analysis of selected markers was thereafter performed. Among the targets identified, periostin, an extracellular matrix protein, presented a significant 3.3-fold higher mRNA expression in progression compared to reversal group. Furthermore, independent of blood pressure, periostin was strongly correlated with plasma creatinine, proteinuria and renal blood flow, hallmarks of hypertensive renal disease severity. Periostin staining was predominant in the injured regions, both in experimental hypertensive and human nephropathy.These results identify periostin as a previously unrecognized marker associated with disease progression and regression in hypertensive nephropathy and suggest measuring periostin may be a sensitive tool to evaluate severity, progression and response to therapy in human kidney disease associated to hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chronic kidney disease  IEP 10041032protein:increased expression:kidney:RGD 
chronic kidney disease  ISOPOSTN (Homo sapiens)10041032; 10041032protein:increased expression:kidney:RGD 
Hypertensive Nephropathy disease_progressionISOPostn (Rattus norvegicus)10041032; 10041032mRNA and protein:increased expression:kidney:RGD 
Hypertensive Nephropathy disease_progressionIEP 10041032mRNA and protein:increased expression:kidney:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Postn  (periostin)

Genes (Mus musculus)
Postn  (periostin, osteoblast specific factor)

Genes (Homo sapiens)
POSTN  (periostin)


Additional Information