Down regulation of CD147 boosts the premature senescence in human skin fibroblasts by destroying the redox balance and inhibiting klotho

Xie, Hongfu; Lei-shan, Liu; Shi, Wei; Xiao, Xiao; Tian, Liming; Jian, Dan; Chen, Xiang; Li, Ji

doi:10.1016/j.jdermsci.2011.09.010

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…Our data suggest that mature and undifferentiated fibroblasts may be responsible for the expression of Klotho in the adventitia. This is supported by recent studies that have demonstrated the expression of Klotho in: 1) normal human skin fibroblasts [ 70 ], 2) synovial fibroblasts [ 71 ], and 3) MRC-5 human primary fibroblast cell line [ 72 ]. Fibroblasts are the most abundant cells in the adventitia and upon activation secrete a number of cytokines, chemokines and growth factors, produce extracellular matrix, and communicate with neural cells and cells of hemopoietic origin.…”

Section: Discussionsupporting

confidence: 60%

Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats

Ritter

Zhang

Delmez

et al. 2015

Kidney International

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Klotho plays an important role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Klotho is highly expressed in the kidney and parathyroid glands, but its presence in the vasculature is debated. Renal Klotho is decreased in CKD, but the effect of uremia on Klotho in other tissues is not defined. The effect of vitamin D receptor activator therapy in CKD on expression of Klotho in various tissues is also in debate. In uremic rats (surgical 5/6th nephrectomy model), we compared 3-months of treatment with and without paricalcitol on Klotho immunostaining in the kidney, parathyroid glands and aorta. With uremia, Klotho was unchanged in the parathyroid, significantly decreased in the kidney (66%) and the intimal-medial area of the aorta (69%), and significantly increased in the adventitial area of the aorta (67%) compared with controls. Paricalcitol prevented the decrease in Klotho in the kidney, increased expression in the parathyroid (31%), had no effect in the aortic media, but blunted the increase of Klotho in aortic adventitia. We propose that fibroblasts are responsible for expression of Klotho in the adventitia. In hyperplastic human parathyroid tissue from uremic patients, Klotho was higher in oxyphil compared with chief cells. Thus, under our conditions of moderate CKD and mild-to-moderate hyperphosphatemia in rats, the differential expression of Klotho and its regulation by paricalcitol in uremia is tissue-dependent.

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Section: Discussionsupporting

confidence: 60%

Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats

Ritter

Zhang

Delmez

et al. 2015

Kidney International

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“…And blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism [60]. Depletion of CD147 sensitizes human malignant melanoma cells to hydrogen peroxide-induced oxidative stress [16]. H2O2 has been shown to induce senescence in normal human skin fibroblasts, in our group we investigated the molecular influences and mechanisms of CD147 on H2O2-induced cellular senescence.…”

Section: The Role Of Cd147 In Malignant Melanomamentioning

confidence: 99%

“…While under oxidative stress conditions induced by H2O2, CD147 silencing exacerbated cellular senescence by increasing ROS accumulation and destroying the intrinsic antioxidant defenses. This process might be related to the klotho protein, a newly discovered anti-aging protein [16]. Since CD147 could promote the production and secretion of MMPs from skin fibroblasts, which is the major component of the microenvironment of MM [27], CD147 is potentially implicated in the development and progression of MM.…”

Section: The Role Of Cd147 In Malignant Melanomamentioning

confidence: 99%

Repressing CD147 is a novel therapeutic strategy for malignant melanoma

Zhou

et al. 2017

Oncotarget

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CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM.

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Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies

Mencke

Olauson

Hillebrands

2017

Advanced Drug Delivery Reviews

108

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Klotho is a membrane-bound protein predominantly expressed in the kidney, where it acts as a permissive co-receptor for Fibroblast Growth Factor 23. In its shed form, Klotho exerts anti-fibrotic effects in several tissues. Klotho-deficient mice spontaneously develop fibrosis and Klotho deficiency exacerbates the disease progression in fibrotic animal models. Furthermore, Klotho overexpression or supplementation protects against fibrosis in various models of renal and cardiac fibrotic disease. These effects are mediated at least partially by the direct inhibitory effects of soluble Klotho on TGFβ1 signaling, Wnt signaling, and FGF2 signaling. Soluble Klotho, as present in the circulation, appears to be the primary mediator of anti-fibrotic effects. Similarly, through inhibition of the TGFβ1, Wnt, FGF2, and IGF1 signaling pathways, Klotho also inhibits tumorigenesis. The Klotho promoter gene is generally hypermethylated in cancer, and overexpression or supplementation of Klotho has been found to inhibit tumor growth in various animal models. This review focuses on the protective effects of soluble Klotho in inhibiting renal fibrosis and fibrosis in distant organs secondary to renal Klotho deficiency. We also discuss the structure-function relationships of Klotho domains and biological effects in the context of potential targeted treatment strategies.

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Down regulation of CD147 boosts the premature senescence in human skin fibroblasts by destroying the redox balance and inhibiting klotho

Cited by 6 publications

References 8 publications

Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats

Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats

Repressing CD147 is a novel therapeutic strategy for malignant melanoma

Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies

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