Clinical Significance of Fibroblast-Specific Protein-1 Expression on Podocytes in Patients with Focal Segmental Glomerulosclerosis

Samejima, Ken-ichi; Nakatani, Katsunori; Suzuki, Daisuke; Asai, Osamu; Sakan, Hirokazu; Yoshimoto, Shuhei; Yamaguchi, Yukinari; Matsui, Masaru; Akai, Yasuhiro; Toyoda, Masao; Iwano, Masayuki; Saito, Yoshihiko

doi:10.1159/000334184

Cited by 10 publications

(4 citation statements)

References 46 publications

(31 reference statements)

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“…In the human GBM, together with collagen IV, collagen I has been identified . Moreover, there is a strong link between collagen I deposition and glomerulosclerosis and fibrosis both as source and implication of cellular impairment (e.g., refs and ). The identified peptides represent a fragment rather than the entire chain; this could be explained by enhanced proteolysis in AS or the already developing fibrosis in this early stage.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Alterations in the Serum of COL(IV)A3^–/^– Mice as Early Biomarkers of Alport Syndrome

et al. 2015

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The efficiency of the inhibition of the angiotensin converting enzyme, the most widely used therapy for the Alport syndrome, depends on the onset of the therapy-the earlier the better. Hence, early progressive biomarkers are urgently required to allow for preclinical diagnosis, an early start of possible therapy as well as the monitoring of this therapy. In the present study, an improved comprehensive and precise proteomic approach has been applied to the serum of juvenile Alport-mice, nontreated and treated, and wild-type controls of various ages to search for biomarkers. With a total of 2542 stringently altered proteins, the serum composition clearly shows a dependency on age, that is, stage, and therapy. Initially, the serum constituents indicate an enhanced extracellular matrix remodeling, cell damage, and the production of particular acute phase proteins. A panel of 15 potential biomarker candidates has been identified. In later stages, renal filtration failure and systemic acute phase reaction determine the composition of the serum; an effect that is well-known for manifested human Alport syndrome. With a small number of mouse urine samples, for example, the proteomic results for gelsolin could be verified using ELISA. Once verified in man, these early biomarkers would allow for a sensitive and specific diagnosis of the Alport syndrome in children as well as facilitate the monitoring of a possible therapy.

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Section: Discussionmentioning

confidence: 99%

Preclinical Alterations in the Serum of COL(IV)A3^–/^– Mice as Early Biomarkers of Alport Syndrome

et al. 2015

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“…EMT has been suggested to play a role in progression of CKD on multiple levels, including podocyte damage and loss in DN (40) and FSGS (41). The RNA level of FSP1 as a marker of EMT was found to be significantly increased in laser captured glomerular compartment of DN or FSGS patients, in comparison with MCD patients.…”

Section: Definition Of Ckd and Ckd Progressionmentioning

confidence: 99%

Genomic biomarkers for chronic kidney disease

Ju¹,

Smith²,

Kretzler³

2012

Translational Research

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Chronic kidney disease (CKD) remains a major challenge in nephrology and for public health care, affecting 14–15% of the adult U.S. population and consuming significant health care resources. In the next 20 years, the number of patients with end stage renal disease is projected to increase by 50%. Ideal biomarkers that allow early identification of CKD patients at high risk of progression are urgently needed for early and targeted treatment to improve patient care. Recent success of integrating molecular approaches for personalized management of neoplastic diseases, including diagnosis, staging, prognosis, treatment selection and monitoring, has strongly encouraged kidney researchers to pursue molecular definitions of patients with kidney disease. Challenges for molecular marker identification in CKD are a high degree of cellular heterogeneity of the kidney and the paucity of human tissue availability for molecular studies. Despite these limitations potential molecular biomarker candidates have been uncovered at multiple levels along the genome – phenome continuum. Here we will review the identification and validation of potential genomic biomarker candidates of CKD and CKD progression in clinical studies. The challenges in predicting CKD progression, as well as the promises and opportunities resulting from a molecular definition of CKD will be discussed.

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“…Moreover, the frequency of FSP1 + podocytes in the urine has been linked to disease severity ( 8 ). FSP1 + podocytes have also been found in the glomeruli of FSGS patients ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Podocyte Dedifferentiation: A Specialized Process for a Specialized Cell

2014

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The podocyte is one of the two cell types that contribute to the formation of the glomerular filtration barrier (GFB). It is a highly specialized cell with a unique structure. The key feature of the podocyte is its foot processes that regularly interdigitate. A structure known as the slit diaphragm can be found bridging the interdigitations. This molecular sieve comprises the final layer of the GFB. It is well accepted that the podocyte is the target cell in the pathogenesis of nephrotic syndrome. In nephrotic syndrome, the GFB no longer restricts the passage of macromolecules and protein is lost into the urine. A number of phenotypic and morphological changes are seen in the diseased podocyte and in the literature these have been described as an epithelial–mesenchymal transition (EMT). However, there is a growing appreciation that this term does not accurately describe the changes that are seen. Definitions of type-2 EMT are based on typical epithelial cells. While the podocyte is known as a visceral epithelial cell, it is not a typical epithelial cell. Moreover, podocytes have several features that are more consistent with mesenchymal cells. Therefore, we suggest that the term podocyte disease transformation is more appropriate.

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Clinical Significance of Fibroblast-Specific Protein-1 Expression on Podocytes in Patients with Focal Segmental Glomerulosclerosis

Cited by 10 publications

References 46 publications

Preclinical Alterations in the Serum of COL(IV)A3^–/^– Mice as Early Biomarkers of Alport Syndrome

Preclinical Alterations in the Serum of COL(IV)A3^–/^– Mice as Early Biomarkers of Alport Syndrome

Genomic biomarkers for chronic kidney disease

Podocyte Dedifferentiation: A Specialized Process for a Specialized Cell

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Clinical Significance of Fibroblast-Specific Protein-1 Expression on Podocytes in Patients with Focal Segmental Glomerulosclerosis

Cited by 10 publications

References 46 publications

Preclinical Alterations in the Serum of COL(IV)A3–/– Mice as Early Biomarkers of Alport Syndrome

Preclinical Alterations in the Serum of COL(IV)A3–/– Mice as Early Biomarkers of Alport Syndrome

Genomic biomarkers for chronic kidney disease

Podocyte Dedifferentiation: A Specialized Process for a Specialized Cell

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Product

Resources

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Preclinical Alterations in the Serum of COL(IV)A3^–/^– Mice as Early Biomarkers of Alport Syndrome

Preclinical Alterations in the Serum of COL(IV)A3^–/^– Mice as Early Biomarkers of Alport Syndrome