Identification of platelet-derived growth factor C as a mediator of both renal fibrosis and hypertension

Roeyen, Claudia R.C. van; Martin, Ina V.; Drescher, Ana; Schuett, Katharina; Hermert, Daniela; Raffetseder, Ute; Otten, Stephanie; Buhl, Eva Miriam; Braun, Gerald S.; Kuppe, Christoph; Liehn, Elisa A.; Weiskirchen, Ralf; Eriksson, Ulf; Groß, Oliver; Eitner, Frank; Floege, Jürgen; Ostendorf, Tammo

doi:10.1016/j.kint.2018.11.031

Cited by 18 publications

(10 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These renoprotective effects of PDGF-CC were accompanied by a prominent improvement of hypertension in these mice. Additional experiments further supported this finding, suggesting a novel role of PDGF-CC in the regulation of blood pressure by directly acting on arterial vessels and the angiotensin system ( 71 ). The second PDGF receptor, PDGR-β, is another well-known mediator of fibrosis.…”

Section: Repair and Modulation Of Kidney Fibrosismentioning

confidence: 72%

“…Recent studies identified novel roles and supported translational relevance of PDGF in CKD and renal fibrosis. Inhibition of the PDGF-CC isoform, a ligand of the PDGFRα, using neutralizing antibodies and genetic deletion, significantly ameliorated renal fibrosis and disease progression in Col4a3 deficient mice, a murine model of genetic progressive glomerular disease closely resembling the human Alport syndrome ( 71 ). These renoprotective effects of PDGF-CC were accompanied by a prominent improvement of hypertension in these mice.…”

Section: Repair and Modulation Of Kidney Fibrosismentioning

confidence: 99%

See 1 more Smart Citation

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

Organ fibrogenesis is characterized by a common pathophysiological final pathway independent of the underlying progressive disease of the respective organ. This makes it particularly suitable as a therapeutic target. The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was hosted from 2009 to 2021 by the Medical Faculties of RWTH Aachen University and the University of Bonn. This consortium had the ultimate goal of discovering new common but also different fibrosis pathways in the liver and kidneys. It finally successfully identified new mechanisms and established novel therapeutic approaches to interfere with hepatic and renal fibrosis. This review covers the consortium's key kidney-related findings, where three overarching questions were addressed: (i) What are new relevant mechanisms and signaling pathways triggering renal fibrosis? (ii) What are new immunological mechanisms, cells and molecules that contribute to renal fibrosis?, and finally (iii) How can renal fibrosis be modulated?

show abstract

Section: Repair and Modulation Of Kidney Fibrosismentioning

confidence: 72%

Section: Repair and Modulation Of Kidney Fibrosismentioning

confidence: 99%

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…PDGF-C activity must be tightly controlled, and uncontrolled PDGF-C expression has been reported to be associated with numerous pathological conditions, such as choroidal neovascularization [ 95 ], chronic myocarditis [ 96 ], glomerulosclerosis [ 64 ], tissue fibrosis [ 12 , 15 , 97 – 99 ], atherosclerosis [ 100 ] and various tumours [ 11 , 98 , 101 – 106 ].…”

Section: Regulation Of Pdgf-c Expressionmentioning

confidence: 99%

“…When PDGFR-β is co-expressed with PDGFR-α, it can be engaged by PDGF-C as well [9]. Studies from the past 20 years or so have demonstrated important roles of PDGF-C in diverse biological processes, such as development, tumour growth, angiogenesis, wound healing, tissue remodelling, fibrosis, atherosclerosis, metabolism and stem/progenitor cell regulation [5,[10][11][12][13][14][15][16]. In this review, however, we mainly discuss the roles and expressions of PDGF-C and its receptors in human and murine development and stem cells.…”

Section: Introductionmentioning

confidence: 99%

Expression and function of PDGF-C in development and stem cells

et al. 2021

View full text Add to dashboard Cite

Platelet-derived growth factor C (PDGF-C) is a relatively new member of the PDGF family, discovered nearly 20 years after the finding of platelet-derived growth factor A (PDGF-A) and platelet-derived growth factor B (PDGF-B). PDGF-C is generally expressed in most organs and cell types. Studies from the past 20 years have demonstrated critical roles of PDGF-C in numerous biological, physiological and pathological processes, such as development, angiogenesis, tumour growth, tissue remodelling, wound healing, atherosclerosis, fibrosis, stem/progenitor cell regulation and metabolism. Understanding PDGF-C expression and activities thus will be of great importance to various research disciplines. In this review, however, we mainly discuss the expression and functions of PDGF-C and its receptors in development and stem cells.

show abstract

“…Among them, transforming growth factor (TGF)-β1 is considered to be the most important fibrogenic factor, which initiates the occurrence and accelerates the progress of fibrosis (12). In addition, recent reports also found that a number of other factors, including platelet-derived growth factor (PDGF), Smad3, connective tissue growth factor and angiotensin II, enhanced the constituents of the ECM (13,14). Although the mechanism behind the formation and development of renal fibrosis has been extensively studied, effective treatment strategies has yet to be found (15,16).…”

Section: Introductionmentioning

confidence: 99%

Poricoic acid A suppresses TGF‑β1‑induced renal fibrosis and proliferation via the PDGF‑C, Smad3 and MAPK pathways

Yao

Jia

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

Renal interstitial fibrosis is the most important pathological process in chronic renal failure. Previous studies have shown that poricoic acid A (PAA), the main chemical constituent on the surface layer of the mushroom Poria cocos, has protective effects against oxidative stress and acute kidney injury. The present study aimed to investigate the potential roles of PAA on the pathological process of renal fibrosis and the associated molecular mechanism. The NRK-49F cell line was treated with transforming growth factor-β1 (TGF-β1) with or without PAA or platelet-derived growth factor C (PDGF-C). Cell Counting Kit-8 assay, western blotting and 5-ethynyl-2'-deoxyuridine immunofluorescence staining were performed to examine cell growth, protein expression and cell proliferation, respectively. Data from the present study showed that 10 µM PAA attenuated TGF-β1-induced NRK-49F cell extracellular matrix (ECM) accumulation, fibrosis formation and proliferation. Renal fibrosis with the activation of Smad3 and mitogen-activated protein kinase (MAPK) pathways were also inhibited by PAA treatment. PDGF-C reversed the inhibitory effects of PAA on TGF-β1-induced renal fibroblast proliferation and activation of the Smad3/MAPK pathway. The present study suggested that suppression of TGF-β1-induced renal fibroblast ECM accumulation, fibrosis formation and proliferation by PAA is mediated via the inhibition of the PDGF-C, Smad3 and MAPK pathways. The present findings not only revealed the potential anti-fibrotic effects of PAA on renal fibroblasts, but also provided a new insight into the prevention of fibrosis formation via regulation of the PDGF-C, Smad3 and MAPK signaling pathways.

show abstract

Identification of platelet-derived growth factor C as a mediator of both renal fibrosis and hypertension

Cited by 18 publications

References 57 publications

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

Expression and function of PDGF-C in development and stem cells

Poricoic acid A suppresses TGF‑β1‑induced renal fibrosis and proliferation via the PDGF‑C, Smad3 and MAPK pathways

Contact Info

Product

Resources

About