Connective tissue growth factor, matrix regulation, and diabetic kidney disease

McLennan, Susan V.; Abdollahi, Maryam; Twigg, Stephen M.

doi:10.1097/mnh.0b013e32835b4889

Cited by 14 publications

(9 citation statements)

References 86 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interactions lead to the activation of intracellular signaling pathways and the activation of transcription factors triggered inflammatory mediators and growth factors release. These in turn mediated extracellular matrix (ECM) protein accumulation, vessel permeability alteration, and proteinuria [6, 7]. Previous treatment of DN focused on aggressive control of hyperglycemia and blood pressure.…”

Section: Introductionmentioning

confidence: 99%

“…Previous treatment of DN focused on aggressive control of hyperglycemia and blood pressure. Currently, glucose-dependent pathways emerged as an important strategy to retard the progression of DN [6]. Several in vitro and in vivo studies have shown DN amelioration by managing the hyperglycemia-induced oxidative stress, inflammation, and lipid accumulation [8, 9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

New Insight into the Molecular Drug Target of Diabetic Nephropathy

Soetikno

Arozal

Louisa

et al. 2014

International Journal of Endocrinology

View full text Add to dashboard Cite

Diabetic nephropathy (DN) lowered quality of life and shortened life expectancy amongst those affected. Evidence indicates interaction between advanced glycation end products (AGEs), activated protein kinase C (PKC) and angiotensin II exacerbate the progression of DN. Inhibitors of angiotensin-converting enzyme (ACEIs), renin angiotensin aldosterone system (RAAS), AGEs, and PKC have been tested for slowing down the progression of DN. The exact molecular drug targets that lead to the amelioration of renal injury in DN are not well understood. This review summarizes the potential therapeutic targets, based on putative mechanism in the progression of the disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New Insight into the Molecular Drug Target of Diabetic Nephropathy

Soetikno

Arozal

Louisa

et al. 2014

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Moreover, CTGF is able to interact with receptors on cells, including integrins, tyrosine receptor kinase A, lowdensity lipoprotein receptor-related protein (LRP), and heparan sulfate proteoglycans [115]. It has pro-inflammatory functions and it may mediate diabetic nephropathy pathogenesis [116]. In a study on streptozotocin (STZ)-induced diabetic C57BL/6J mice and type 2 diabetic ob/ob mice, CTGF levels in the blood and urine were increased in these diabetic mice.…”

Section: Ccn Family Proteins In Obesity and Associated Diseasesmentioning

confidence: 98%

Extracellular matrix in obesity – cancer interactions

Barreto¹,

Hopkins²,

Bhowmick³

et al. 2015

Hormone Molecular Biology and Clinical Investigation

View full text Add to dashboard Cite

Obesity or overweight is a risk factor for several health disorders such as type 2 diabetes, hypertension, and certain cancers. Furthermore, obesity affects almost all body systems including the extracellular matrix (ECM) by generating a pro-inflammatory environment, which are associated with abnormal secretions of several cytokines or hormonal substances, for example, insulin-like growth factors (IGFs), leptin, and sex hormones. These chemical mediators most likely have a great impact on the ECM. Accumulating evidence suggests that both obesity and ECM can influence tumor growth and progression through a number of chemical mediators. Conversely, cells in the connective tissue, namely fibroblasts and macrophages, support and aggravate the inflammatory situation in obesity by releasing several cytokines or growth factors such as vascular endothelial growth factor, epidermal growth factor, and transforming growth factor-beta (TGF-β). A wide range of functions are performed by TGF-β in normal health and pathological conditions including tumorigenesis. Breast cancer in postmenopausal women is a classic example of obesity-related cancer wherein several of these conditions, for example, higher levels of pro-inflammatory cytokines, impairment in the regulation of estrogen and growth factors, and dysregulation of different ECM components may favor the neoplastic process. Aberrant expressions of ECM components such as matrix metalloproteinases or matricellular proteins in both obesity and cancer have been reported by many studies. Nonstructural matricellular proteins, viz., thrombospondins, secreted protein acidic and rich in cysteine (SPARC), and Cyr61-CTGF-Nov (CCN), which function as modulators of cell-ECM interactions, exhibit protean behavior in cancer. Precise understanding of ECM biology can provide potential therapeutic targets to combat obesity-related pathologies.

show abstract

“…22,23 Its overproduction was proposed to play a major role in many fibrotic diseases, including renal fibrosis. 24,25 Ito 26 first studied pathogenic role of CTGF in DN and found that its expression was correlated with the severity and progression of kidney injury. Using transgenic mice, Yokoi et al 27 provided direct evidence of CTGF in the pathogenesis of DN, especially in podocytes injury.…”

Section: Discussionmentioning

confidence: 99%

CTGF mediates high-glucose induced epithelial–mesenchymal transition through activation of β-catenin in podocytes

Dai

Zhang

et al. 2016

Renal Failure

View full text Add to dashboard Cite

Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, China ABSTRACT Objective: It is known that connective tissue growth factor (CTGF) and b-catenin are involved in DN; however, the underlying molecular mechanisms remain unknown. Here we hypothesized that podocytes undergo epithelial-mesenchymal transition (EMT) in high-glucose condition and CTGF mediates high-glucose induced EMT by activating b-catenin in podocytes. Methods: The differentiated podocytes were cultured and divided into three groups: the normal glucose group (5 mmol/L glucose), the high-glucose group (30 mmol/L glucose), and the osmotic control group (5 mmol/L glucose supplemented with 25 mmol/L mannitol). The morphology of cultured podocytes was observed under phase contrast microscopy. To study the relevant markers of EMT, as well as CTGF and b-catenin, the mRNA and protein expressions were analyzed by realtime PCR and western blotting, respectively. In addition, the effects of inhibition CTGF by anti-CTGF antibody on high-glucose-induced EMT and b-catenin expression in podocytes were studied. Results: High glucose not only induced phenotypic transition of podocytes but also increased the expression of CTGF and b-catenin. Under high-glucose condition, podocytes underwent EMT, which were demonstrated by downregulation of nephrin and upregulation of desmin. Moreover, high-glucose-induced EMT and b-catenin overexpression in podocytes were attenuated by anti-CTGF antibody. Conclusion: CTGF and b-catenin are involved in the EMT of podocytes in diabetes. CTGF mediates high-glucose induced EMT through activation of b-catenin in podocytes. CTGF inhibition may protect podocytes from EMT in diabetes.ARTICLE HISTORY

show abstract

Connective tissue growth factor, matrix regulation, and diabetic kidney disease

Abstract: Recent publications implicate CCN-2 as both an evolving marker and mediator of diabetic nephropathy.

Cited by 14 publications

References 86 publications

New Insight into the Molecular Drug Target of Diabetic Nephropathy

New Insight into the Molecular Drug Target of Diabetic Nephropathy

Extracellular matrix in obesity – cancer interactions

CTGF mediates high-glucose induced epithelial–mesenchymal transition through activation of β-catenin in podocytes

Contact Info

Product

Resources

About