Phosphoinositide 3-kinase/protein kinase B/periostin mediated platelet-derived growth factor-induced cell proliferation and extracellular matrix production in lupus nephritis

Zhao, Xue; Hao, Jun; Duan, Huijun; Rong, Zanhua; Li, Fan

doi:10.1177/1535370216668050

Cited by 20 publications

(20 citation statements)

References 24 publications

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“…Fibronectin, a ubiquitous glycoprotein of ECM that plays a role in tissue remodeling is considered as a decisive contributing factor to switch from normal wound healing to deregulated fibrosis ( Petrini et al, 2017 ). Excess fibronectin is produced from endothelial cells and fibroblasts upon stimulation of growth factors including platelet derived growth factor and TGF-β1 ( Hocevar et al, 1999 ; Zhao et al, 2017 ). Hence, the role of WFA on fibronectin was evaluated and we observed dramatic decrease in expression of fibronectin in WFA treated HFL1 cells.…”

Section: Discussionmentioning

confidence: 99%

An Adaptogen: Withaferin A Ameliorates in Vitro and in Vivo Pulmonary Fibrosis by Modulating the Interplay of Fibrotic, Matricelluar Proteins, and Cytokines

et al. 2018

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Pulmonary fibrosis (PF) is chronic lung disease with only two FDA approved clinically available drugs, with limited safety profile. Inadequate therapy motivated us to explore the effect of vimentin inhibitor Withaferin A, as an anti-fibrotic agent against TGF-β1-induced in vitro fibrotic events and Bleomycin induced in vivo fibrosis with an emphasis on epithelial to mesenchymal transition (EMT), extracellular matrix deposition (ECM), inflammation, and angiogenesis. In vitro EMT and fibrotic events were induced by TGF-β1 in alveolar epithelial cells and human fetal lung fibroblasts followed by treatment with Withaferin A (0.25, 0.5, and 1 μM concentrations) to explore its anti-fibrotic effects. In vivo potential of Withaferin A (2 and 4 mg/kg) was assessed in murine model of Bleomycin induced PF. All the parameters and molecular studies related to PF were performed at the end of treatment period. Withaferin A treatment reduced the progression of PF by modulating the EMT related cell markers both in vivo and in vitro. Withaferin A ameliorated the expression of inflammatory cytokines including NF-κB p65, IL-1β and TNF-α, as well as attenuated the expression of pro-fibrotic proteins including CTGF, collagen 1A2, collagen 3A1, and fibronectin. Expression of angiogenic factors like VEGF, FAK, p38 MAPK, and PLC-γ1 were also inhibited by Withaferin A. Phosphorylation of Smad 2/3 induced by TGF-β1 and Bleomycin were significantly inhibited. Withaferin A suppressed expression of pro-inflammatory, pro-fibrotic, and pro-angiogenic mediators and also reduced the ECM deposition. In a nutshell, Withaferin A could probably prove as an efficient and potential therapeutic against PF.

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Section: Discussionmentioning

confidence: 99%

An Adaptogen: Withaferin A Ameliorates in Vitro and in Vivo Pulmonary Fibrosis by Modulating the Interplay of Fibrotic, Matricelluar Proteins, and Cytokines

et al. 2018

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“…Fibronectin is critical for fibrotic progression in glomerulonephritis and is distributed widely in the mesangial matrix, glomerular, and tubular basement membranes, and Bowman's capsule. The formation of glomerular fibronectin is enhanced both in patients and mice with active LN (90, 91). We have demonstrated that anti-dsDNA IgG contributes to renal fibrosis by downregulating suppressor of cytokine signaling 1 (SOCS1) and activating Janus kinase/signal transducer and activator of transcription 1 signals, which modulate the expression of profibrotic genes, transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor B, and connective tissue growth factor (92, 93).…”

Section: The Pathogenicity Of Anti-dsdna Antibodiesmentioning

confidence: 99%

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

2019

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Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin, specificity, and pathogenicity of anti-dsDNA antibodies have been studied from a wider perspective. These autoantibodies have been suggested to contribute to multiple end-organ injuries, especially to lupus nephritis, in patients with SLE. Moreover, serum levels of anti-DNA antibodies fluctuate with disease activity in patients with SLE. By directly binding to self-antigens or indirectly forming immune complexes, anti-dsDNA antibodies can accumulate in the glomerular and tubular basement membrane. These autoantibodies can also trigger the complement cascade, penetrate into living cells, modulate gene expression, and even induce profibrotic phenotypes of renal cells. In addition, the expression of suppressor of cytokine signaling 1 is reduced by anti-DNA antibodies simultaneously with upregulation of profibrotic genes. Anti-dsDNA antibodies may even participate in the pathogenesis of SLE by catalyzing hydrolysis of certain DNA molecules or peptides in cells. Recently, anti-dsDNA antibodies have been explored in greater depth as a therapeutic target in the management of SLE. A substantial amount of data indicates that blockade of pathogenic anti-dsDNA antibodies can prevent or even reverse organ damage in murine models of SLE. This review focuses on the recent research advances regarding the origin, specificity, classification, and pathogenicity of anti-dsDNA antibodies and highlights the emerging therapies associated with them.

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“…At the end of the last century, Troyer et al ( 29 ) showed that a calorie-restricted diet was successful in modulating the key inflammatory ligand platelet-derived growth factor (PDGF) subunit A and the thrombin receptor, resulting in the suppression of murine lupus nephritis. Quite recently, the direct mechanism of this finding has been explained, elucidating the role of PDGF as a growth factor that regulates cell proliferation and is responsible for mesangial proliferation, periostin formation and progressive glomerulosclerosis ( 30 ).…”

Section: Macronutrientsmentioning

confidence: 99%

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

et al. 2020

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.

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Phosphoinositide 3-kinase/protein kinase B/periostin mediated platelet-derived growth factor-induced cell proliferation and extracellular matrix production in lupus nephritis

Cited by 20 publications

References 24 publications

An Adaptogen: Withaferin A Ameliorates in Vitro and in Vivo Pulmonary Fibrosis by Modulating the Interplay of Fibrotic, Matricelluar Proteins, and Cytokines

An Adaptogen: Withaferin A Ameliorates in Vitro and in Vivo Pulmonary Fibrosis by Modulating the Interplay of Fibrotic, Matricelluar Proteins, and Cytokines

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

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