RGD Reference Report - Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic change induced by transforming growth factor-beta1. - Rat Genome Database

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Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic change induced by transforming growth factor-beta1.

Authors: Guo, W  Xu, H  Chen, J  Yang, Y  Jin, JW  Fu, R  Liu, HM  Zha, XL  Zhang, ZG  Huang, WY 
Citation: Guo W, etal., Mol Cell Biochem. 2007 Jan;295(1-2):167-77. Epub 2006 Oct 17.
RGD ID: 2292410
Pubmed: PMID:17043753   (View Abstract at PubMed)
DOI: DOI:10.1007/s11010-006-9286-4   (Journal Full-text)

Prohibitin (PHB), a potential tumor suppressor, has been shown to inhibit cell proliferation by repressing E2F-mediated transcription. But little is known about the role of PHB involved in tubulointerstitial fibrosis (TIF). Here, for the first time, we found PHB protein was positively expressed at normal renal tissues, strongly down-regulated in renal biopsy specimens, and negatively correlated with the expression of alpha-smooth-muscle actin (alpha-SMA) and with the degrees of tubulointerstitial lesions. Transforming growth factor-beta1 (TGF-beta1) is the most important profibrotic cytokine in the process of TIF and capable of inducing cell phenotypic change of interstitial fibroblasts characterized by the de novo expression of alpha-SMA. Confocal microscopy showed majority of PHB is located at cytoplasm as well as at nucleus in rat kidney fibroblasts cell (NRK-49F). As we found that PHB protein and mRNA expression were down-regulated in NRK-49F cells following TGF-beta1 stimulation. We used transient transfection to over-express PHB protein and found that cells with increased PHB levels had a significant reduction in the percentage entering cell cycle and abolished de novo expression of alpha-SMA following TGF-beta1 stimulation. Therefore, over-expression of PHB suppresses renal interstitial fibroblasts proliferation and cell phenotypic change induced by TGF-beta1, which indicates PHB as a potential therapeutic target to halt the progression of TIF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Fibrosis  IEP 2292410associated with Glomerulonephritis more ...RGD 
Fibrosis  ISOPHB1 (Homo sapiens)2292410; 2292410associated with Glomerulonephritis more ...RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Acta2  (actin alpha 2, smooth muscle)
Phb1  (prohibitin 1)

Genes (Mus musculus)
Phb1  (prohibitin 1)

Genes (Homo sapiens)
PHB1  (prohibitin 1)


Additional Information