ECM Characterization Reveals a Massive Activation of Acute Phase Response during FSGS

Bukosza, Éva Nóra; Kornauth, Christoph; Hummel, Karin Anna; Schachner, Helga; Huttary, Nicole; Krieger, Sigurd; Nöbauer, Katharina; Oszwald, André; Razzazi-Fazeli, Ebrahim; Kratochwill, Klaus; Aufricht, Christoph; Szénási, Gábor; Hamar, Péter; Gebeshuber, Christoph A.

doi:10.3390/ijms21062095

Cited by 15 publications

(19 citation statements)

References 47 publications

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“…The hyalinelike accumulating material within the glomerular ECM stained positive for fibrinogen (Figure 2B). Besides fibrinogens, several other APPs and complement-related proteins were abundant in the glomerular ECM as detected by MS [14]. The most exciting model of renal ischemia-reperfusion injury-induced fibrosis is the result of our recent demonstration that fibrosis progression is halted by delayed removal of the contralateral kidney.…”

Section: Acute (Aki) and Chronic Kidney Disease (Ckd)mentioning

confidence: 96%

“…Thus, APPs can contribute to local defense responses and repair mechanisms [ 11 ]. We have demonstrated by proteomic analysis a complex local production of several APPs in different tissues upon injury, such as electromagnetic heating of tumor cells [ 12 ], or acute hypoxic [ 13 ] or chronic fibrotic injury of the kidney [ 14 ]. In all of these studies [ 6 , 12 , 13 , 14 ], >50 percent of the top 20 upregulated proteins were APPs, as detected by next-generation sequencing (NGS) and verified by nanostring, PCR or mass spectrometry (MS).…”

Section: Mainmentioning

confidence: 99%

“…We have demonstrated by proteomic analysis a complex local production of several APPs in different tissues upon injury, such as electromagnetic heating of tumor cells [ 12 ], or acute hypoxic [ 13 ] or chronic fibrotic injury of the kidney [ 14 ]. In all of these studies [ 6 , 12 , 13 , 14 ], >50 percent of the top 20 upregulated proteins were APPs, as detected by next-generation sequencing (NGS) and verified by nanostring, PCR or mass spectrometry (MS). Thus, we propose that local APP production may be a similar, organized, ancient stress response to the well-known HSR.…”

Section: Mainmentioning

confidence: 99%

“…Following damage of tubular epithelial cells (TEC), the development of the highly differentiated form of TEC can be disturbed during the regenerative processes leading to pathological changes of intrinsic regulatory processes. Several factors, such as TGF-beta [ 6 , 12 , 13 , 14 ], miR-21, HIF-1alpha, etc., are considered protective and stimulate regenerative processes following acute tubular injury, but sustained elevation of these factors is the major driving force of chronic scarring and fibrosis (CKD) leading to eventual renal failure. We investigated AKI and CKD in three mouse models: endotoxin (LPS)-induced renal ischemia [ 13 ], renal ischemia-reperfusion-induced fibrosis [ 18 ] and miR-193 transgene-induced fibrosis [ 14 ].…”

Section: Mainmentioning

confidence: 99%

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A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

Hamar

2022

IJMS

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The prevailing general view of acute-phase proteins (APPs) is that they are produced by the liver in response to the stress of the body as part of a systemic acute-phase response. We demonstrated a coordinated, local production of these proteins upon cell stress by the stressed cells. The local, stress-induced APP production has been demonstrated in different tissues (kidney, breast cancer) and with different stressors (hypoxia, fibrosis and electromagnetic heat). Thus, this local acute-phase response (APR) seems to be a universal mechanism. APP production is an ancient defense mechanism observed in nematodes and fruit flies as well. Local APP production at the tissue level is also supported by sporadic literature data for single proteins; however, the complex, coordinated, local appearance of this stress response has been first demonstrated only recently. Although a number of literature data are available for the local production of single acute-phase proteins, their interpretation as a local, coordinated stress response is new. A better understanding of the role of APPs in cellular stress response may also be of diagnostic/prognostic and therapeutic significance.

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Section: Acute (Aki) and Chronic Kidney Disease (Ckd)mentioning

confidence: 96%

Section: Mainmentioning

confidence: 99%

Section: Mainmentioning

confidence: 99%

Section: Mainmentioning

confidence: 99%

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A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

Hamar

2022

IJMS

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“…Focal segmental glomerulosclerosis (FSGS) is an important glomerular cause of end-stage kidney disease, and is associated with a high risk of disease recurrence after kidney transplantation[ 1 - 5 ]. Approximately 30% of patients[ 6 , 7 ] develop recurrent FSGS following kidney transplantation, with studies reporting a range between 17% and 55%[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Rituximab or plasmapheresis for prevention of recurrent focal segmental glomerulosclerosis after kidney transplantation: A systematic review and meta-analysis

Boonpheng¹,

Hansrivijit²,

Mao³

et al. 2021

WJT

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BACKGROUND Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results. AIM To assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy. METHODS This meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included ‘FSGS,’ ’steroid-resistant nephrotic syndrome’, ‘rituximab,’ and ‘plasmapheresis,’. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case–control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model. RESULTS Eleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I 2 = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I 2 = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival. CONCLUSION Overall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.

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Urinary SPP1 has potential as a non‐invasive diagnostic marker for focal segmental glomerulosclerosis

Ye,

Xu,

Xue

et al. 2023

FEBS Open Bio

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Focal segmental glomerulosclerosis (FSGS) is a type of chronic glomerular nephropathy showing characteristic glomerular sclerosis, diagnosed by kidney biopsy. However, it is difficult and expensive to monitor disease progression with repeated renal biopsy in clinical practice, and thus here we explored the feasibility of urine biomarkers as non‐invasive diagnostic tools. We downloaded scRNA‐seq datasets of 20 urine cell samples and 3 kidney tissues and obtained two gene lists encoding extracellular proteins for bioinformatic analysis; in addition, we identified key EP‐Genes by immunohistochemical staining and performed bulk RNA sequencing with 12 urine samples. We report that urine cells and kidney cells were correlated. A total of 64 EP‐Genes were acquired by intersecting genes of distal tubular cluster with extracellular proteins. Function enrichment analysis showed that EP‐Genes might be involved in the immune response and extracellular components. Six key EP‐Genes were identified and correlated with renal function. IMC showed that key EP‐Genes were located mainly in tubules. Cross verification and examination of a urine RNAseq dataset showed that SPP1 had diagnostic potential for FSGS. The presence of urine SPP1 was primarily associated with macrophage infiltration in kidney, and the pathogenesis of FSGS may be related to innate immunity. Urinary cells seemed to be strongly similar to kidney cells. In summary, SPP1 levels reflect renal function and may have potential as a biomarker for non‐invasive diagnosis of FSGS.

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ECM Characterization Reveals a Massive Activation of Acute Phase Response during FSGS

Cited by 15 publications

References 47 publications

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

Rituximab or plasmapheresis for prevention of recurrent focal segmental glomerulosclerosis after kidney transplantation: A systematic review and meta-analysis

Urinary SPP1 has potential as a non‐invasive diagnostic marker for focal segmental glomerulosclerosis

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