Renal Fibrosis in Lupus Nephritis

Sciascia, Savino; Cozzi, Martina; Barinotti, Alice; Radin, Massimo; Cecchi, Irene; Fenoglio, Roberta; Mancardi, Daniele; Jones, Georgia Wilson; Rossi, Daniela; Roccatello, Dario

doi:10.3390/ijms232214317

Cited by 18 publications

(25 citation statements)

References 106 publications

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“…26 The involvement of renal tubulointerstitium can lead to pathological changes such as renal tubular epithelial cells (RTECs) injury, 16 inflammation, hypoxia, ECM deposition, and epithelial to mesenchymal transition (EMT), leading to renal tubular fibrosis and atrophy. 17,26,31 Figure 2 shows the possible relevant mechanism of the pathologic progression of lupus nephritis to renal fibrosis.…”

Section: Pathology and Classification Of Lnmentioning

confidence: 99%

“…13 The complex inflammatory environment gradually leads to proliferation of mesangial, endothelial, and epithelial cells, podocyte injury and loss of foot process, proliferation of myofibroblasts, and increased formation and deposition of extracellular matrix (ECM), ultimately leading to glomerular dysfunction and sclerosis. 16,17…”

Section: Pathology and Classification Of Lnmentioning

confidence: 99%

Figure 2.Pathologic progression of Lupus nephritis. anti-dsDNA: anti-double-stranded DNA antibodies; DNA-ENAS: DNA-extractable nuclear antigen antibodies; anti-RNP: anti-ribonucleoproteins; MCs: Mesangial cells; ECM: extracellular matrix; ICD: immune complex deposition; TMA: thrombotic microangiopathosis; AS: arteriosclerosis; NNV: non-inflammatory necrotizing vascular disease; TRV: true renal vasculitis; RTECs: renal tubular epithelial cells; EMT: epithelial to mesenchymal transition.…”

Section: Pathology and Classification Of Lnmentioning

confidence: 99%

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Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury

Liu

Zhou

2023

Lupus

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Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus and is also a major predictor of poor prognosis and mortality. Lupus nephritis has the characteristics of insidious onset, complex pathological types, rapid progression of organ damage, and easy recurrence. Currently, kidney damage in lupus nephritis is usually assessed based on urine analysis, renal biopsy, and glomerular filtration rates. However, they all have certain limitations, making it difficult to diagnose lupus nephritis early and assess its severity and progression. With the rapid development of functional magnetic resonance, multiple functional imaging techniques are expected to provide more useful information for the pathophysiological development, early diagnosis, progression, prognosis, and renal function evaluation of lupus nephritis. This article reviews the principle of multiple functional magnetic resonance imaging and the research status of evaluating renal function in lupus nephritis.

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Section: Pathology and Classification Of Lnmentioning

confidence: 99%

Section: Pathology and Classification Of Lnmentioning

confidence: 99%

Section: Pathology and Classification Of Lnmentioning

confidence: 99%

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Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury

Liu

Zhou

2023

Lupus

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“…Shenkang injection is composed of four extracts of herb plants, namely, Astragalus, Salvia, Rhubarb, and Safflower, which has the effects of purging fu‐organs and clearing turbidity (Tongfuxiezhuo), promoting blood circulation and removing blood stasis (Huoxuehuayu), and invigorating qi and relieving dampness (Buqilishi) and has shown a remarkable therapeutic effect on CRF (Wei et al., 2022). Renal fibrosis, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is a common pathological change in the progression of chronic kidney disease toward renal failure and end‐stage renal disease (Sciascia et al., 2022). Previous studies had shown that the main active components of Shenkang Injection include hydroxy saffron yellow pigment A, tanshinol, rheum emodin, and astragaloside IV (Xu et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Renal fibrosis, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is a common pathological change in the progression of chronic kidney disease toward renal failure and end-stage renal disease (Sciascia et al, 2022). Previous studies had shown that the main active components of Shenkang Injection include hydroxy saffron yellow pigment A, tanshinol, rheum emodin, and astragaloside IV (Xu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic–pharmacodynamic modeling of the active components of Shenkang injection in rats with chronic renal failure and its protective effect on damaged renal cells

Zhou,

Wang,

Xia

et al. 2023

Biopharm & Drug Disp

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The study aimed to explore the pharmacokinetic and pharmacodynamic alterations of the active components of Shenkang injection (i.e. hydroxy saffron yellow pigment A [HSYA], tanshinol, rheum emodin, and astragaloside IV) in rats with chronic renal failure (CRF), and establish a pharmacokinetic–pharmacodynamic model (PK‐PD model) in order to provide a scientific and theoretical basis for the rational clinical use of Shenkang injection. Sprague–Dawley (SD) rats were randomly divided into a normal group, model group, and Shenkang injection group. A rat model of CRF was induced by adenine gavage and then followed by drug administration via tail vein injection. Orbital blood was collected at different timepoints and the blood concentrations of the four active components were measured by UHPLC‐Q‐Orbitrap HRMS. Serum levels of creatinine (Scr), urea nitrogen (BUN), and uric acid (UA) were determined using an automatic biochemical analyzer. A PK‐PD model was established, and DAS 3.2.6 software was used for model fitting as well as statistical analysis. TGF‐β1 was utilized to induce normal rat kidney cells to construct a renal fibrosis model to investigate the protective effect of the pharmacological components on renal fibrosis. The pharmacokinetic analysis of hydroxy saffron yellow pigment A, tanshinol, rheum emodin, and astragaloside IV based on UHPLC‐Q‐Orbitrap HRMS was stable. The linear regression equations for the four active components were as follows: Y = 0.031X + 0.0091 (R2 = 0.9986) for hydroxy saffron yellow pigment A, Y = 0.0389X + 0.164 (R2 = 0.9979) for tanshinol, Y = 0.0257X + 0.0146 (R2 = 0.9973) for rheum emodin, and Y = 0.0763X + 0.0139 (R2 = 0.9993) for astragaloside IV, which indicated good linear relationships. The methodological investigation was stable, with the interday and intraday precision RSD <10%. Meanwhile, the recoveries ranged between 90% and 120%, in accordance with the requirements for in vivo analysis of drugs. Compared with the model group, the levels of Scr, BUN, and UA were significantly decreased after 20 min in the Shenkang injection group (p < 0.01). The PK‐PD model showed that the four active components in the Shenkang injection group could fit well with the three effect measures (i.e. Scr, BUN, and UA), with the measured values similar to the predicted values. The cell model of renal fibrosis showed that the connective tissue growth factor and FN1 protein expression levels were significantly lower in the Shenkang injection group than those in the model group, and the cell fibrosis was improved. The established method for in vivo analysis of Shenkang injection was highly specific, with good separation of the components and simple operation. The total statistical moment could well integrate the pharmacokinetic parameters of the four active components. After treatment with Shenkang injection, all indexes in the administered group improved and showed significant inhibition of renal cell fibrosis in vitro. This study could provide scientific reference ideas for the clinical rational use of traditional Chinese medicine.

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Cordyceps cicadae ameliorates inflammatory responses, oxidative stress, and fibrosis by targeting the PI3K/mTOR‐mediated autophagy pathway in the renal of MRL/lpr mice

Yang,

Zhang,

Dong

et al. 2024

Immunity Inflam & Disease

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BackgroundThe vast majority of systemic lupus erythematosus patients develop lupus nephritis (LN) with severe renal manifestations, such as inflammatory responses, oxidative stress, and fibrosis. The purpose of this research was to investigate Cordyceps cicadae as a potential therapeutic target for treating inflammatory responses, oxidative stress, and fibrosis in LN.MethodsThe effects of C. cicadae on lupus symptoms in mice with LN were determined. MRL/lpr mice were treated with C. cicadae (4 g/kg/day, i.e., CC group, n = 8) or an equal volume of saline (model group, n = 8), and MRL/MP mice were treated with an equal volume of saline (control group, n = 8). Renal function indices, renal pathology, inflammatory markers, oxidative stress markers, and renal interstitial fibrosis levels were evaluated after C. cicadae treatment. Western blot analysis was performed to investigate the effect of C. cicadae on the expression of fibrosis biomarkers and the phosphatidylinositol 3‐kinase (PI3K)/mammalian target of rapamycin (mTOR)‐mediated autophagy pathway in the renal tissues of mice.ResultsC. cicadae ameliorated renal lesions, the inflammatory response, and oxidative stress damage in MRL/lpr mice. C. cicadae treatment inhibited renal fibrosis (16.31 ± 4.16 vs. 31.25 ± 5.61) and downregulated the expression of the fibrosis biomarkers alpha‐smooth muscle actin, fibronectin, and collagen I (COL I) in the kidneys of MRL/lpr mice. In addition, further research showed that the PI3K/mTOR‐mediated autophagy pathway was involved in C. cicadae‐mediated effects on renal fibrosis in MRL/lpr mice. Furthermore, the therapeutic effect of C. cicadae on repairing renal fibrosis and damage in MRL/lpr mice was abolished by the PI3K agonist 740 Y‐P.ConclusionsThe findings of the present research showed that C. cicadae could alleviate inflammatory responses, oxidative stress, and fibrosis in the renal tissues of mice with LN by targeting the PI3K/mTOR‐mediated autophagy pathway.

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Renal Fibrosis in Lupus Nephritis

Cited by 18 publications

References 106 publications

Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury

Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury

Pharmacokinetic–pharmacodynamic modeling of the active components of Shenkang injection in rats with chronic renal failure and its protective effect on damaged renal cells

Cordyceps cicadae ameliorates inflammatory responses, oxidative stress, and fibrosis by targeting the PI3K/mTOR‐mediated autophagy pathway in the renal of MRL/lpr mice

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