C-Reactive Protein Promotes Diabetic Kidney Disease in db/db Mice via the CD32b-Smad3-mTOR signaling Pathway

You, Yong‐Ke; Huang, Xiao‐Ru; Chen, Haiyong; Lyu, Xiafei; Liu, Huafeng; Lan, Hui‐Yao

doi:10.1038/srep26740

Cited by 48 publications

(83 citation statements)

References 49 publications

(76 reference statements)

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“…As demonstrated in our previous studies, CRP can activate ERK/p38 MAPK and NF‐κB signalling to promote inflammation in kidney tissue . Other studies have shown that CRP can induce plasminogen activator inhibitor‐1 (PAI‐1) expression via p38 MAPK in endothelial cells, suggesting its pathogenic role in disturbing the delicate balance in thrombosis and inflammation.…”

Section: Pathogenic Mechanisms Of Crp In Ageingsupporting

confidence: 57%

“…Importantly, CRP also activated mTOR signalling at 30 minutes via a Smad3‐dependent mechanism as Smad3‐bound mTOR and CRP‐induced mTOR signalling was abolished by a specific Smad3 inhibitor. Finally, we found that CRP‐induced renal fibrosis through a CD32b‐Smad3‐mTOR pathway, as blockade of mTOR signalling with rapamycin inhibited CRP‐induced connective tissue growth factor (CTGF) and collagen I expression …”

Section: Pathogenic Mechanisms Of Crp In Ageingmentioning

confidence: 93%

“…Our group has also investigated intervening on the TGF‐β/Smad3 pathway in diabetes mellitus, a common disorder in the elderly characterised by chronic renal and vascular injury, inflammation and elevated CRP. Using a mouse model of type 2 diabetes in human CRPtg (CRPtg‐db/db), we found that the animals developed more severe type 2 diabetes, higher levels of fasting blood glucose, more severe microalbuminuria and more progressive renal inflammation and fibrosis, compared with non‐diabetic or control animals . Diabetes in CRPtg‐db/db mice was associated with over‐activation of CRP‐CD32b, NF‐κB, TGF‐β/Smad3 and mechanistic target of rapamycin (mTOR) signalling.…”

Section: Pathogenic Mechanisms Of Crp In Ageingmentioning

confidence: 99%

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C‐reactive protein and ageing

Tang

Fung

et al. 2017

Clin Exp Pharma Physio

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SummaryIncreasing evidence shows that C-reactive protein (CRP) is not only an inflammatory biomarker but also an important risk factor associated with ageing-related diseases including cardiovascular disease, hypertension, diabetes mellitus, and kidney disease.Recent studies have demonstrated that CRP is pathogenic in a number of diseases including hypertensive cardiovascular and kidney complications, diabetic nephropathy, and acute and chronic kidney diseases. It is well known that CRP binds its receptor, CD32/CD64, to induce the process of inflammation by activating the NF-κB signalling pathway. In addition, CRP mediates tissue fibrosis in a number of cardiovascular and kidney diseases by activating TGF-β/Smad signalling via TGF-β1-dependent and independent mechanisms. Furthermore, CRP is able to activate mTOR signalling in the diabetic conditions. Our recent studies also revealed that CRP impairs cell regeneration by causing the G1 cell cycle arrest and promotes ageing via a Smad3-dependent

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Section: Pathogenic Mechanisms Of Crp In Ageingsupporting

confidence: 57%

Section: Pathogenic Mechanisms Of Crp In Ageingmentioning

confidence: 93%

Section: Pathogenic Mechanisms Of Crp In Ageingmentioning

confidence: 99%

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C‐reactive protein and ageing

Tang

Fung

et al. 2017

Clin Exp Pharma Physio

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“…Total RNA was isolated from the renal tissues and cultured HK‐2 cells using TRIzol reagent from Invitrogen according to the manufacturer's instructions, and real‐time PCR was performed using Bio‐Rad IQ SYBR Green Supermix with Option 2 (Bio‐Rad, Hercules, CA) as previously described . The primers used in this study for mouse IL‐1β, TNF‐a, TGF‐β1, a‐SMA, collagen I and fibronectin mRNAs have been described previously . The housekeeping gene β‐actin was used as an internal control.…”

Section: Methodsmentioning

confidence: 99%

“…To examine the changes in renal morphology, we stained formalinfixed, paraffin-embedded sections (3 µm) with haematoxylin and eosin or a Masson's trichrome staining kit (ScyTek Laboratories, West Logan, UT) according to the manufacturer's instructions and as previously described. 29,30 Immunohistochemistry was performed in paraffin sections using a microwave-based antigen retrieval method. 31 The primary antibodies used in this study included antibodies against Cybernetics, Bethesda, MD) as described previously.…”

Section: Morphological and Immunohistochemical Analysismentioning

confidence: 99%

Petchiether A attenuates obstructive nephropathy by suppressing TGF‐β/Smad3 and NF‐κB signalling

You

Luo

Wang

et al. 2019

J Cellular Molecular Medi

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Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor‐β1 (TGF‐β1)/Smad3‐driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small‐molecule meroterpenoid from Ganoderma , as a potential inhibitor of TGF‐β1‐induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin‐1β and tumour necrosis factor‐α) and reducing extracellular matrix deposition (α‐smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF‐κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down‐regulated the expression of the fibrotic marker collagen I in TGF‐β1‐treated renal epithelial cells. Further, we found that petA dose‐dependently suppressed Smad3‐responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF‐β/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF‐β/Smad3 signalling.

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Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

et al. 2019

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Studies investigating the associations between genetic or environmental factors and Parkinson's disease (PD) have uncovered a number of factors shared with cardiovascular disease, either as risk factors or manifestations of cardiovascular disease itself. Older age, male sex, and possibly type 2 diabetes are examples. On the other hand, coffee consumption and physical activity are each associated with a lower risk of both PD and cardiovascular disease. This observation raises questions about the underlying pathophysiological links between cardiovascular disease and PD. There is evidence for common mechanisms in the areas of glucose metabolism, cellular stress, lipid metabolism, and inflammation. On the other hand, smoking and total/low‐density lipoprotein cholesterol appear to have opposite associations with cardiovascular disease and PD. Thus, it is uncertain whether the treatment of cardiovascular risk factors will impact on the onset or progression of PD. The available data suggest that a nuanced approach is necessary to manage risk factors such as cholesterol levels once the associations are better understood. Ultimately, the choice of therapy may be tailored to a patient's comorbidity profile. This review presents the epidemiological evidence for both concordant and discordant associations between cardiovascular disease and PD, discusses the cellular and metabolic processes that may underlie these links, and explores the implications this has for patient care and future research. © 2019 International Parkinson and Movement Disorder Society

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C-Reactive Protein Promotes Diabetic Kidney Disease in db/db Mice via the CD32b-Smad3-mTOR signaling Pathway

Cited by 48 publications

References 49 publications

C‐reactive protein and ageing

C‐reactive protein and ageing

Petchiether A attenuates obstructive nephropathy by suppressing TGF‐β/Smad3 and NF‐κB signalling

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

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