Transduction of PTEN Proteins Using the Tat Domain Modulates TGF-β1–Mediated Signaling Pathways and Transdifferentiation in Subconjunctival Fibroblasts

Chung, Eun Jee; Jung, Sun-Ah; Lee, Seung-Jae; Chee, Hee Youn; Sohn, Yong Ho; Lee, Joon‐Hyung

doi:10.1167/iovs.11-8491

Cited by 16 publications

(7 citation statements)

References 40 publications

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“…There is a wealth of literature documenting the critical role of PTEN loss in fibrogenesis. In many fibrotic diseases, myofibroblasts have diminished PTEN expression but overexpression of PTEN or its reconstitution results in suppression of AKT and consequent fibrogenesis . In many fibrotic diseases, PTEN expression is reduced or simply absent .…”

Section: Mutations Of Cancer Driver Genes In Endometriosis and Their mentioning

confidence: 99%

“…In many fibrotic diseases, myofibroblasts have diminished PTEN expression 161 but overexpression of PTEN or its reconstitution results in suppression of AKT and consequent fibrogenesis. [167][168][169] In many fibrotic diseases, PTEN expression is reduced or simply absent. [170][171][172][173][174][175] Aberrant PTEN/AKT signaling inactivates FOXO3a, a proapoptotic factor, promoting fibrosis.…”

Section: Ptenmentioning

confidence: 99%

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Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

Guo

2018

Reprod Medicine & Biology

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BackgroundOne recent study reports cancer driver mutations in deep endometriosis, but its biological/clinical significance remains unclear. Since the natural history of endometriosis is essentially gradual progression toward fibrosis, it is thus hypothesized that the six driver genes reported to be mutated in endometriosis (the RP set) may play important roles in fibrogenesis but not necessarily malignant transformation.MethodsExtensive PubMed search to see whether RP and another set of driver genes not yet reported (NR) to be mutated in endometriosis have any roles in fibrogenesis. All studies reporting on the role of fibrogenesis of the genes in both RP and NR sets were retrieved and evaluated in this review.ResultsAll six RP genes were involved in various aspects of fibrogenesis as compared with only three NR genes. These nine genes can be anchored in networks linking with their upstream and downstream genes that are known to be aberrantly expressed in endometriosis, piecing together seemingly unrelated findings.ConclusionsGiven that somatic driver mutations can and do occur frequently in physiologically normal tissues, it is argued that these mutations in endometriosis are not necessarily synonymous with malignancy or premalignancy, but the result of enormous pressure for fibrogenesis.

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Section: Mutations Of Cancer Driver Genes In Endometriosis and Their mentioning

confidence: 99%

Section: Ptenmentioning

confidence: 99%

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

Guo

2018

Reprod Medicine & Biology

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“…Accumulating evidence suggests that miR-21 promotes cell proliferation via the activation of PTEN/AKT signaling in cancer cells [14,15]. Previous studies showed that transducing the Tat-PTEN fusion protein into subconjunctival fibroblasts results in the suppression of Akt phosphorylation and further suppresses activation of myofibroblasts [16].…”

Section: Introductionmentioning

confidence: 99%

miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling

Liu

Xiang-wang

et al. 2014

IJMS

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The precise role of nucleus pulposus cell proliferation in the pathogenesis of intervertebral disc degeneration remains to be elucidated. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, may regulate cell proliferation in many pathological conditions. Here, we showed that miR-21 was significantly upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues that were isolated from patients with idiopathic scoliosis and that miR-10b levels were associated with disc degeneration grade. Moreover, bioinformatics target prediction identified PTEN as a putative target of miR-21. miR-21 inhibited PTEN expression by directly targeting the 3′UTR, and this inhibition was abolished through miR-21 binding site mutations. miR-21 overexpression stimulated cell proliferation and AKT signaling pathway activation, which led to cyclin D1 translation. Additionally, the increase in proliferation and cyclin D1 expression induced by miR-21 overexpression was almost completely blocked by Ly294002, an AKT inhibitor. Taken together, aberrant miR-21 upregulation in intervertebral disc degeneration could target PTEN, which would contribute to abnormal nucleus pulposus cell proliferation through derepressing the Akt pathway. Our study also underscores the potential of miR-21 and the PTEN/Akt pathway as novel therapeutic targets in intervertebral disc degeneration.

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“…[3][4][5] One of the main reasons for the failure of trabeculectomy is excessive subconjunctival fibrosis (scar formation) due to the proliferation of Tenon's fibroblasts and the subsequent increase in the synthesis of extracellular matrix (ECM) and collagen contraction. 6,7 Although transforming growth factor-beta 1 (TGF-b1) is known to play a crucial role in scar formation, the detailed mechanisms associated with its function have not yet been elucidated. 8 Several recently published papers have demonstrated the regulatory effects of microRNA (miRNA) on TGF-b and have rekindled interest in TGF-b-mediated fibrosis.…”

mentioning

confidence: 99%

TGF-β1 Stimulates Human Tenon's Capsule Fibroblast Proliferation by miR-200b and its Targeting of p27/kip1 and RND3

Tong

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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Transduction of PTEN Proteins Using the Tat Domain Modulates TGF-β1–Mediated Signaling Pathways and Transdifferentiation in Subconjunctival Fibroblasts

Cited by 16 publications

References 40 publications

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling

TGF-β1 Stimulates Human Tenon's Capsule Fibroblast Proliferation by miR-200b and its Targeting of p27/kip1 and RND3

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