Epidermal Growth Factor Induces Proliferation of Hair Follicle-Derived Mesenchymal Stem Cells Through Epidermal Growth Factor Receptor-Mediated Activation of ERK and AKT Signaling Pathways Associated with Upregulation of Cyclin D1 and Downregulation of p16

Bai, Tingting; Liu, Feilin; Zou, Fei; Zhao, Guifang; Jiang, Yixu; Liu, Li; Shi, Jiahong; Hao, Deshun; Zhang, Qi; Zheng, Tong; Zhang, Yingyao; Liu, Mingsheng; Li, Shilun; Qi, Liangchen; Liu, Jin Yu

doi:10.1089/scd.2016.0234

Cited by 67 publications

(63 citation statements)

References 47 publications

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“…Furthermore, we demonstrated that inhibition of ERK/MAPK pathway could promote the senescence of endosteal osteoprogenitors and block the survival and proliferation ability of osteoprogenitors induced by EGF treatment. This is consistent with a recent report that EGFR signaling promotes proliferation of hair follicle-derived mesenchymal stem cells through ERK1/2 and suppresses the expression of the p16 INK4a (35). Therefore, advancing age is associated with a decrease in EGFR/ERK signaling whereby endosteal osteoprogenitors undergo senescence, leading to decreased endosteal bone formation and cortical bone degeneration.…”

Section: Discussionsupporting

confidence: 92%

The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone

Liu

Xie

et al. 2019

FASEB j.

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So far, there has been no effective cure for osteoporotic cortical bone, the most significant change in long bone structure during aging and the main cause of bone fragility fractures, because its underlying molecular and cellular mechanisms remain largely unknown. We used 3‐ and 15‐mo‐old mice as well as 15‐mo‐old mice treated with vehicle and gefitinib to evaluate structural, cellular, and molecular changes in cortical bone. We found that the senescence of osteoprogenitors was increased, whereas the expression of phosphorylated epidermal growth factor receptor (EGFR) on the endosteal surface of cortical bone down‐regulated in middle‐aged 15‐mo‐old mice compared with young 3‐mo‐old mice. Further decreasing EGFR signaling by gefitinib treatment in middle‐aged mice resulted in promoted senescence of osteoprogenitors and accelerated cortical bone degeneration. Moreover, inhibiting EGFR signaling suppressed the expression of enhancer of zeste homolog 2 (Ezh2), the repressor of cell senescence‐inducer genes, through ERK1/2 pathway, thereby promoting senescence in osteoprogenitors. Down‐regulated EGFR signaling plays a physiologically significant role during aging by reducing Ezh2 expression, leading to the senescence of osteoprogenitors and the decline in bone formation on the endosteal surface of cortical bone.—Liu, G., Xie, Y., Su, J., Qin, H., Wu, H., Li, K., Yu, B., Zhang, X. The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone. FASEB J. 33, 11137–11147 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 92%

The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone

Liu

Xie

et al. 2019

FASEB j.

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“…A recent study using hair follicle-derived mesenchymal stem cells found that EGF significantly increased proliferation as well as phosphorylation of EGFR, ERK, and AKT in a time- and dose-dependent manner, increased cyclin D1 levels, and shifted cells from G1 to the S and G2 phases. In addition, AG1478, LY294002, or U0126 prevented EGF-induced cell proliferation and reduced p-EGFR, p-AKT, and p-ERK1/2 expression [35]. Together with our findings, these data suggest that the overall pattern of EGFR activities in ES resembles that found in mesenchymal stem cells from healthy donors.…”

Section: Discussionsupporting

confidence: 82%

Epidermal Growth Factor Receptor Regulation of Ewing Sarcoma Cell Function

et al. 2018

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Objective: Ewing sarcoma (ES) is a type of childhood cancer probably arising from stem mesenchymal or neural crest cells. The epidermal growth factor receptor (EGFR) acts as a driver oncogene in many types of solid tumors. However, its involvement in ES remains poorly understood. Methods: Human SK-ES-1 and RD-ES ES cells were treated with EGF, the EGFR inhibitor tyrphostin (AG1478), or phosphoinositide 3-kinase (PI3K) or extracellular-regulated kinase (ERK)/mitogen-activated kinase (MAPK) inhibitors. Cell proliferation survival, cycle, and senescence were analyzed. The protein content of possible targets of EGFR manipulation was measured by Western blot. Results: Cell proliferation and survival were increased by EGF and inhibited by AG1478. The EGFR inhibitor also altered the cell cycle, inducing arrest in G1 and increasing the sub-G1 population, reduced polyploidy and increased the population of senescent cells. In addition, AG1478 reduced the levels of phosphorylated AKT (p-AKT), ERK, p-ERK, cyclin D1, and brain-derived neurotrophic factor (BDNF), while enhancing p53 levels. Cell proliferation was also impaired by inhibitors of PI3K or ERK, alone or combined with AG1478. Conclusions: Our findings reveal novel aspects of EGFR regulation of ES cells and provide early evidence for antitumor activities of EGFR inhibitors in ES.

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“…Another limitation is that HFT differentiation was only analyzed using Oil Red O staining, not differentiation markers or fluorescence-activated cell sorting analysis. Additionally, previous studies have reported other potential molecular pathways that may be associated with the proliferation (33)(34)(35)(36)(37) and differentiation of HFTs, including the Wnt signal transduction pathway, forkhead box P1-mediated oxidative stress and epidermal growth factor receptor/extracellular signal-regulated kinases/AKT, c-Jun N-terminal kinases/c-Jun and TGF-β pathways (38). The present study only investigated the PI3K/AKT signaling pathway in HFTs.…”

Section: Discussionmentioning

confidence: 90%

Long non‑coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway

Cai

Zheng

et al. 2018

Mol Med Report

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Long non-coding RNAs (lncRNAs) are defined as non-coding transcripts (>200 nucleotides) that serve important roles in the proliferation and differentiation of stem cells. Hair follicle stem cells (HFTs) have multidirectional differentiation potential and are able to differentiate into skin, hair follicles and sebaceous glands, serving a role in skin wound healing. The aim of the present study was to analyze the regulatory role of lncRNA AK015322 (IncRNA5322) in HFTs and the potential mechanism of IncRNA5322‑mediated differentiation of HFTs. The results demonstrated that lncRNA5322 transfection promoted proliferation and differentiation in HFTs. It was identified that lncRNA5322 transfection upregulated the expression and phosphorylation of phosphoinositide 3‑kinase (PI3K) and protein kinase B (AKT) in HFTs. It was also observed that lncRNA5322 transfection upregulated microRNA (miR)‑21 and miR‑21 agonist (agomir‑21) eliminated lncRNA5322‑induced expression and phosphorylation of PI3K and AKT. The present study also demonstrated that agomir‑21 blocked IncRNA5322‑induced expression and phosphorylation of PI3K and AKT in HFTs. The results indicated that agomir‑21 transfection also suppressed the IncRNA5322‑induced proliferation and differentiation of HFTs. In conclusion, the results of the present study suggest that lncRNA5322 is able to promote the proliferation and differentiation of HFTs by targeting the miR‑21‑mediated PI3K‑AKT signaling pathway in HFTs.

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Epidermal Growth Factor Induces Proliferation of Hair Follicle-Derived Mesenchymal Stem Cells Through Epidermal Growth Factor Receptor-Mediated Activation of ERK and AKT Signaling Pathways Associated with Upregulation of Cyclin D1 and Downregulation of p16

Cited by 67 publications

References 47 publications

The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone

The role of EGFR signaling in age‐related osteoporosis in mouse cortical bone

Epidermal Growth Factor Receptor Regulation of Ewing Sarcoma Cell Function

Long non‑coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway

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