Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis

Fu, Haiyan; Tian, Yuan; Zhou, Lili; Zhou, Dong; Tan, Roderick J.; Stolz, Donna B.; Liu, Youhua

doi:10.1681/asn.2016020165

Cited by 101 publications

(111 citation statements)

References 48 publications

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“…TNC is an extracellular matrix protein, whose de novo expression follows very rapidly in response to various stress stimuli like e.g. ischemia reperfusion and has been shown to promote renal interstitial fibroblast proliferation that may eventually favor the premature development of kidney fibrosis after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Role of erythrocytes in short‐term rewarming kidney perfusion after cold storage

Minor

Horn

Paul³

2019

Artificial Organs

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Short term normothermic reconditioning by machine perfusion after cold storage has shown beneficial effects in renal transplantation models. Systematic investigations concerning the inclusion of washed erythrocytes as oxygen carriers are lacking in this context. Porcine kidneys were subjected to 20 h of static cold storage. Prior to reperfusion, grafts were put on a machine for 2 h of oxygenated (95% O2; 5% CO2) rewarming perfusion. In one group (n = 6) washed erythrocytes were added to the perfusate after temperature has reached 20°C; the other group (n = 6) was run without additives. Control kidneys (n = 6) were immediately reperfused without treatment. Upon reperfusion in vitro, a more than twofold improvement of renal clearance of creatinine, urinary protein loss, fractional excretion of sodium, efficiency of oxygen utilization (TNa/VO2) and a significant reduction of innate immune activation (HMGB1, tenascin C, expression of TLR4) was seen after machine perfusion, compared with the controls. However, no advantage could be obtained by the addition of erythrocytes and inner cortical tissue pO2 always remained above normal values during cell‐free machine perfusion. Our data strongly argue in favor of a rewarming perfusion of cold stored donor kidneys but do not substantiate an indication for adding oxygen carriers in this particular setting.

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Section: Discussionmentioning

confidence: 99%

Role of erythrocytes in short‐term rewarming kidney perfusion after cold storage

Minor

Horn

Paul³

2019

Artificial Organs

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“…It is conceivable that Wnt ligands may not be distributed evenly across renal parenchyma, but could be recruited and concentrated focally by some unrecognized mechanisms, because kidney fibrotic lesion typically initiates at certain focal sites. We recently postulated the concept of the fibrogenic niche, and proposed tenascin‐C (TNC), an ECM glycoprotein, as an organizer of such a functional entity . TNC expression is increased rapidly in fibrotic kidneys and predominantly localizes at the foci rich in fibroblasts in renal interstitium .…”

Section: Recruitment Of Wnt Ligandsmentioning

confidence: 99%

“…We recently postulated the concept of the fibrogenic niche, and proposed tenascin‐C (TNC), an ECM glycoprotein, as an organizer of such a functional entity . TNC expression is increased rapidly in fibrotic kidneys and predominantly localizes at the foci rich in fibroblasts in renal interstitium . Further loss‐ or gain‐of‐function studies have confirmed the role of TNC in organizing a specialized microenvironment that facilitates fibroblast activation and proliferation both in vitro and in vivo.…”

Section: Recruitment Of Wnt Ligandsmentioning

confidence: 99%

New insights into the role and mechanism of Wnt/β‐catenin signalling in kidney fibrosis

Zuo

Liu

2018

Nephrology

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Wnt/β‐catenin is an evolutionarily conserved, developmental signalling pathway that regulates embryogenesis, injury repair and pathogenesis of human diseases. Dysregulated activation of Wnt/β‐catenin is associated with the development and progression of renal fibrotic lesions after injury. Wnt are induced and β‐catenin is activated in various models of experimental chronic kidney disease (CKD) and in human nephropathies. Recent findings indicate that pro(renin) receptor is an amplifier of Wnt/β‐catenin by acting as a downstream target and an obligatory component for its signal transduction. Genetic blockade of Wnt secretion in a cell type‐specific manner uncovers renal tubular epithelium as the major source of Wnt ligands in CKD. Wnt/β‐catenin controls the expression of a wide variety of downstream mediators implicated in kidney fibrosis, such as fibronectin, Snail1, matrix metalloproteinase‐7, hepatocyte growth factor and various components of the renin‐angiotensin system. Targeted inhibition of Wnt/β‐catenin is able to ameliorate kidney fibrotic lesions in pre‐clinical settings. In this review, we summarize recent advances in our understanding of the regulation, signal transduction, role and mechanisms of Wnt/β‐catenin signalling in the pathogenesis of kidney fibrosis. We also discuss the therapeutic potential of targeting this pathway for the treatment of fibrotic CKD.

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“…A recent interesting study proposed a novel role for TN-C as an important component of the fibrogenic niche which facilitates fibroblast proliferation and expansion of fibrosis. The authors showed that TN-C was produced by fibroblasts and localized in fibrogenic foci in two models of kidney fibrosis, while it induced fibroblast proliferation and activation of proliferation-related genes through an integrin/FAK/mitogenactivated protein kinase pathway, both in vivo and in vitro (88).…”

Section: Tenascinsmentioning

confidence: 99%