Identification of Periostin as a Critical Marker of Progression/Reversal of Hypertensive Nephropathy

Guerrot, Dominique; Dussaule, Jean–Claude; Mael-Ainin, Mouna; Xu‐Dubois, Yi‐Chun; Rondeau, Éric; Chatziantoniou, Christos; Placier, Sandrine

doi:10.1371/journal.pone.0031974

Cited by 67 publications

(81 citation statements)

References 30 publications

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“…Various human and experimental renal diseases affect the glomerular podocytes that form the final filtration barrier, leading to proteinuria. [31][32][33] Molecular changes of the slit diaphragm following any pathologic alterations in the podocytes will eventually result in restructuring of the arrangement in the foot process with the fusion of filtration slits and apical shift of the slit diaphragm. [34][35][36] Nestin, an intermediate filament protein primarily identified in neural stem cells, is transiently expressed in the glomerular podocytes of the adult kidney that are linked with the maintenance of the foot process structure.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

Eladl

Elsaed

Atef

et al. 2017

IJNRD

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Background: Several renal disorders affect the glomerular podocytes. Compensatory structural and functional changes have been observed in animals that have undergone unilateral renal ablation. These changes occur as a pliant response to quench the increased functional demand to maintain homeostasis of fluid and solutes. Nestin is an intermediate filament protein present in the glomerular podocytes of the adult kidney and is linked with the maintenance of its foot process structure. Structural changes in the podocytes ultimately restructure the filtration barrier. Very few studies related to the ultrastructural and histopathologic changes of the podocytes are documented. The present study aimed to assess the histopathologic changes at the ultrastructural level in the adapted kidney at different time intervals following unilateral renal ablation in adult rats and its relation with nestin. Methods: Forty-eight rats were divided into four groups (n=12 in each group). The animals of Group A were control naïve rats, while the group B, group C and group D animals underwent left unilateral nephrectomy and the remaining right kidney was removed on days 10, 20 and 30, respectively. Each group included four sham-operated rats, which were sacrificed at the same time as the naïve rats. Each nephrectomized sample was weighed and its sections were subjected to hematoxylin and eosin examination, transmission electron microscopic study as well as immunostaining using the intermediate filament protein nestin. Results: No difference was found between the kidney sections from the control group and the sham-operated groups. A significant increase in the weight of the right kidneys was noted in groups B, C and D (P<0.001). The ultrastructural adaptive changes seen in the glomeruli of group B were subsequently reduced in groups C and D. This finding corresponded to a similar pattern of nestin expression in the podocytes, which showed significant increase in group B followed by reduced expression in groups C and D. Histopathologic and transmission electron microscopic evaluation of group B showed signs of kidney injury. On the other hand, group C animals showed markedly reduced renal adaptive changes and similar changes were also noted in group D. Conclusion: Correlation between nestin expression and the ultrastructural changes confirms that nestin has a role in increasing the mechanical stability of the podocytes in order to enhance their morphologic changes in response to the tensile glomerular capillary wall. However, further studies investigating more remote ultrastructural changes and their relation with nestin expression are needed to confirm this relationship.

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Section: Introductionmentioning

confidence: 99%

Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

Eladl

Elsaed

Atef

et al. 2017

IJNRD

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“…14 We reported that periostin is highly upregulated during disease progression and inversely downregulated during regression in a model of hypertensive renal disease. 15 Although the above results indicate that periostin can be a new biomarker of renal disease progression, whether periostin participates in the development of CKD has not been examined. This hypothesis was investigated in the present study using two complementary approaches: mice lacking periostin (Postn null mice) and in vivo administration of antisense (AS) oligonucleotides (ODNs) in hypertensive rats.…”

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confidence: 96%

Inhibition of Periostin Expression Protects against the Development of Renal Inflammation and Fibrosis

Mael-Ainin

Abed

Conway

et al. 2014

Journal of the American Society of Nephrology

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Increased renal expression of periostin, a protein normally involved in embryonic and dental development, correlates with the decline of renal function in experimental models and patient biopsies. Because periostin has been reported to induce cell differentiation, we investigated whether it is also involved in the development of renal disease and whether blocking its abnormal expression improves renal function and/ or structure. After unilateral ureteral obstruction in wild-type mice, we observed a progressive increase in the expression and synthesis of periostin in the obstructed kidney that associated with the progression of renal lesions. In contrast, mice lacking the periostin gene showed less injury-induced interstitial fibrosis and inflammation and were protected against structural alterations. This protection was associated with a preservation of the renal epithelial phenotype. In vitro, administration of TGF-b to renal epithelial cells increased the expression of periostin several-fold, leading to subsequent loss of the epithelial phenotype. Furthermore, treatment of these cells with periostin increased the expression of collagen I and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery of antisense oligonucleotides to inhibit periostin expression protected animals from L-NAME-induced renal injury. These data strongly suggest that periostin mediates renal disease in response to TGF-b and that blocking periostin may be a promising therapeutic strategy against the development of CKD.

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“…13 We previously reported that periostin expression is highly correlated with disease progression in a model of hypertensive nephropathy, and we subsequently showed that mice lacking periostin are protected against the structural alterations induced by unilateral ureteral obstruction. 14,15 Despite these findings, the mechanisms of induction and function of periostin in renal disease are largely unknown. In this study we investigated these mechanisms in an established chronic renal disease model induced by nephrotoxic serum (NTS) administration.…”

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NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GN

Prakoura

Kavvadas

Kormann

et al. 2016

JASN

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De novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NFkB and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN. Mice lacking expression of periostin displayed preserved renal function and structure during GN. Furthermore, delayed administration of periostin antisense oligonucleotides in wild-type animals with GN reversed already established proteinuria, diminished tissue inflammation, and improved renal structure. Lack of periostin expression also blunted the de novo renal expression of integrin-b3 and phosphorylation of focal adhesion kinase and AKT, known mediators of integrin-b3 signaling that affect cell motility and survival, observed during GN in wild-type animals. In vitro, recombinant periostin increased the expression of integrin-b3 and the concomitant phosphorylation of focal adhesion kinase and AKT in podocytes. Notably, periostin and integrin-b3 were highly colocalized in biopsy specimens from patients with inflammatory GN. These results demonstrate that interplay between periostin and renal inflammation orchestrates inflammatory and fibrotic responses, driving podocyte damage through downstream activation of integrin-b3 signaling. Targeting periostin may be a novel therapeutic strategy for treating CKD.

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Identification of Periostin as a Critical Marker of Progression/Reversal of Hypertensive Nephropathy

Cited by 67 publications

References 30 publications

Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

Inhibition of Periostin Expression Protects against the Development of Renal Inflammation and Fibrosis

NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GN

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