Prognostic value of connective tissue growth factor and c-Myb expression in IgA nephropathy and Henoch-Schönlein purpura—A pilot immunohistochemical study

Mizdrak, Maja; Filipović, Natalija; Vukojević, Katarina; Čapkun, Vesna; Mizdrak, Ivan; Durdov, Merica Glavina

doi:10.1016/j.acthis.2019.151479

Cited by 9 publications

(3 citation statements)

References 23 publications

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“…In our study, c-Myb was, for the first time, analyzed immunohistochemically in kidneys of patients with IgAN/IgA vasculitis and healthy controls. c-Myb was expressed in glomerular epithelial cells, as well as distal tubules [57]. Patients significantly differed from controls, in that c-Myb expression was higher through the entire nephron of patients.…”

Section: C-mybmentioning

confidence: 86%

Emerging Biomarkers for Early Detection of Chronic Kidney Disease

Mizdrak

Kumrić

Kurir

et al. 2022

JPM

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Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to prevent further deterioration of kidney function and to delay adverse outcomes. However, the paucity of early, predictive and noninvasive biomarkers has undermined our ability to promptly detect and treat this common clinical condition which affects more than 10% of the population worldwide. Despite all limitations, kidney function is still measured by serum creatinine, cystatin C, and albuminuria, as well as estimating glomerular filtration rate using different equations. This review aims to provide comprehensive insight into diagnostic methods available for early detection of CKD. In the review, we discuss the following topics: (i) markers of glomerular injury; (ii) markers of tubulointerstitial injury; (iii) the role of omics; (iv) the role of microbiota; (v) and finally, the role of microRNA in the early detection of CKD. Despite all novel findings, none of these biomarkers have met the criteria of an ideal early marker. Since the central role in CKD progression is the proximal tubule (PT), most data from the literature have analyzed biomarkers of PT injury, such as KIM-1 (kidney injury molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), and L-FABP (liver fatty acid-binding protein).

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Section: C-mybmentioning

confidence: 86%

Emerging Biomarkers for Early Detection of Chronic Kidney Disease

Mizdrak

Kumrić

Kurir

et al. 2022

JPM

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“…Besides the classic TGFβ/Smad3 signaling pathway, multiple signaling pathways are dysregulated in fibrotic kidneys. Impaired peroxisome proliferative activated receptor alpha (PPARA), hepatocyte nuclear factor 4 alpha (HNF4A) and activation of nuclear factor kappa-B (NFκB, such as c-Rel), Sex determining region Y-Box 6 (SOX6), early growth response protein 2 (EGR2), c-Myb signaling pathways are associated with progression of renal fibrosis [ 7 – 13 ]. Krüppel-like factors (KLFs) belong to a family of zinc-finger transcription factors, which is a research hotspot in the field of kidney disease and several KLF family members have been identified as important players in renal tubulointerstitial fibrosis [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

SDMA attenuates renal tubulointerstitial fibrosis through inhibition of STAT4

Wang

Chen

et al. 2023

J Transl Med

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Background Renal tubulointerstitial fibrosis is the hallmark of various chronic kidney diseases. Symmetric dimethylarginine (SDMA) is an independent cardiovascular risk factor in patients with chronic kidney diseases, which is mostly excreted through renal tubules. However, the effect of SDMA on kidneys in a pathological condition is currently unknown. In this study, we investigated the role of SDMA in renal tubulointerstitial fibrosis and explored its underlying mechanisms. Methods Mouse unilateral ureteral obstruction (UUO) and unilateral ischemia–reperfusion injury (UIRI) models were established to study renal tubulointerstitial fibrosis. SDMA was injected into kidneys through ureter retrogradely. TGF-β stimulated human renal epithelial (HK2) cells were used as an in vitro model and treated with SDMA. Signal transducer and activator of transcription-4 (STAT4) was inhibited by berbamine dihydrochloride or siRNA or overexpressed by plasmids in vitro. Masson staining and Western blotting were performed to evaluate renal fibrosis. Quantitative PCR was performed to validate findings derived from RNA sequencing analysis. Results We observed that SDMA (from 0.01 to 10 µM) dose-dependently inhibited the expression of pro-fibrotic markers in TGF-β stimulated HK2 cells. Intrarenal administration of SDMA (2.5 µmol/kg or 25 µmol/kg) dose-dependently attenuated renal fibrosis in UUO kidneys. A significant increase in SDMA concentration (from 19.5 to 117.7 nmol/g, p < 0.001) in mouse kidneys was observed after renal injection which was assessed by LC–MS/MS. We further showed that intrarenal administration of SDMA attenuated renal fibrosis in UIRI induced mouse fibrotic kidneys. Through RNA sequencing analysis, we found that the expression of STAT4 was reduced by SDMA in UUO kidneys, which was further confirmed by quantitative PCR and Western blotting analysis in mouse fibrotic kidneys and renal cells. Inhibition of STAT4 by berbamine dihydrochloride (0.3 mg/ml or 3.3 mg/ml) or siRNA reduced the expression of pro-fibrotic markers in TGF-β stimulated HK2 cells. Furthermore, blockage of STAT4 attenuated the anti-fibrotic effect of SDMA in TGF-β stimulated HK2 cells. Conversely, overexpression of STAT4 reversed the anti-fibrotic effect of SDMA in TGF-β stimulated HK2 cells. Conclusion Taken together, our study indicates that renal SDMA ameliorates renal tubulointerstitial fibrosis through inhibition of STAT4.

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“…При последующем наблюдении отмечена прямая корреляция между скоростью прогрессирования нефропатии и экспрессией ФРСТ в клетках канальцев. Авторы данной работы предположили, что ФРСТ может быть новым, ранним и чувствительным маркером возникновения хронической болезни почек [35]. В одно из наиболее крупных исследований ФРСТ при нефрологической патологии было включено 404 пациента, находящихся на гемодиализе.…”

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Connective Tissue Growth Factor in Normal and Pathological Processes

Тополянская

2020

Arhivʺ vnutrennej mediciny

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Modern concepts about the role of connective tissue growth factor in various physiological and pathological processes are described in the review. Connective tissue growth factor regulates a variety of cellular functions, including proliferation, migration, adhesion, differentiation and synthesis of extracellular matrix proteins in cells of different types. This factor is also involved in more complex biological processes of angiogenesis, chondrogenesis, wound healing, fibrosis and oncogenesis. Increased expression of connective tissue growth factor is observed in different cardiovascular and oncological diseases. Potential role of this growth factor in regulation of cellular senescence and aging processes is also discussed.

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Prognostic value of connective tissue growth factor and c-Myb expression in IgA nephropathy and Henoch-Schönlein purpura—A pilot immunohistochemical study

Cited by 9 publications

References 23 publications

Emerging Biomarkers for Early Detection of Chronic Kidney Disease

Emerging Biomarkers for Early Detection of Chronic Kidney Disease

SDMA attenuates renal tubulointerstitial fibrosis through inhibition of STAT4

Connective Tissue Growth Factor in Normal and Pathological Processes

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