TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21

被引：146

作者：

Liu, Ying ^{[1
]}

Li, Yue ^{[2
]}

Li, Ning ^{[1
]}

Teng, Wen ^{[1
]}

Wang, Min ^{[1
]}

Zhang, Yingbo ^{[1
]}

Xiao, Zhibo ^{[1
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 2, Dept Plast & Aesthet Surg, Harbin 150081, Peoples R China

[2] Harbin Med Univ, Affiliated Hosp 2, Dept Gen Surg, Harbin 150081, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

中国国家自然科学基金;

关键词：

HYPERTROPHIC SCAR; MESSENGER-RNA; IN-VITRO; NORMAL SKIN; EXPRESSION; PROTEIN; INVASION; MIR-21; PTEN; PHOSPHATASE;

D O I：

10.1038/srep32231

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

TGF-beta 1, upregulated in keloid tissue, promotes the proliferation, collagen formation and differentiation of dermal fibroblasts. miR-21 is one of microRNAs first found in human genome. The aim of our study is to explore the mechanisms of miR-21 in TGF-beta 1-induced scar fibroblasts proliferation and transdifferentiation. In the present study, first we found that TGF-beta 1 promoted scar fibroblasts proliferation and transdifferentiation via up-regulating miR-21 expression, which could be attenuated when miR-21 was inhibited. Overexpression of miR-21 had similar effect as TGF-beta 1 on proliferation and transdifferentiation. Additionally, TGF-beta 1 increased the expressions and activities of MMP2 and MMP9 in keloid fibroblasts, which was suppressed by miR-21 inhibition. Finally, the results demonstrated that PTEN/AKT signaling pathway played important role in TGF-beta 1-induced transdifferentiation. In conclusion, our study suggests that TGF-beta 1 promotes keloid fibroblasts proliferation and transdifferentiation via up-regulation of miR-21 and PTEN/AKT signalling pathway plays important role in this process, which provides a potential theoretical basis for clinical treatment of skin scars.

引用

页数：9

共 35 条

[11] TGFβ-Stimulated MicroRNA-21 Utilizes PTEN to Orchestrate AKT/mTORC1 Signaling for Mesangial Cell Hypertrophy and Matrix Expansion [J].

Dey, Nirmalya ;

Ghosh-Choudhury, Nandini ;

Kasinath, Balakuntalam S. ;

Choudhury, Goutam Ghosh .

PLOS ONE, 2012, 7 (08)

[12] MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs [J].

Fan, Xuesong ;

Wang, Enshi ;

Wang, Xianyun ;

Cong, Xiangfeng ;

Chen, Xi .

EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2014, 96 (02) :242-249

[13] Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin [J].

Fumagalli, Mara ;

Musso, Tiziana ;

Vermi, William ;

Scutera, Sara ;

Daniele, Roberta ;

Alotto, Daniela ;

Cambieri, Irene ;

Ostorero, Alessia ;

Gentili, Francesca ;

Caposio, Patrizia ;

Zucca, Mario ;

Sozzani, Silvano ;

Stella, Maurizio ;

Castagnoli, Carlotta .

EXPERIMENTAL DERMATOLOGY, 2007, 16 (07) :600-610

[14] MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators [J].

Gabriely, Galina ;

Wurdinger, Thomas ;

Kesari, Santosh ;

Esau, Christine C. ;

Burchard, Julja ;

Linsley, Peter S. ;

Krichevsky, Anna M. .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (17) :5369-5380

[15] IMMUNOLOCALIZATION OF TGF-BETA(1) IN HUMAN HYPERTROPHIC SCAR AND NORMAL DERMAL TISSUES [J].

GHAHARY, A ;

SHEN, YJ ;

SCOTT, PG ;

TREDGET, EE .

CYTOKINE, 1995, 7 (02) :184-190

[16] REGULATION OF COLLAGEN-SYNTHESIS AND MESSENGER-RNA EXPRESSION IN NORMAL AND HYPERTROPHIC SCAR FIBROBLASTS IN-VITRO BY INTERFERON-GAMMA [J].

HARROP, AR ;

GHAHARY, A ;

SCOTT, PG ;

FORSYTH, N ;

UJIFRIEDLAND, A ;

TREDGET, EE .

JOURNAL OF SURGICAL RESEARCH, 1995, 58 (05) :471-477

[17] Transforming Growth Factor-β-Induced Endothelial-to-Mesenchymal Transition Is Partly Mediated by MicroRNA-21 [J].

Kumarswamy, Regalla ;

Volkmann, Ingo ;

Jazbutyte, Virginija ;

Dangwal, Seema ;

Park, Da-Hee ;

Thum, Thomas .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2012, 32 (02) :361-U441

[18]

Li DM, 1997, CANCER RES, V57, P2124

[19]

[刘亚明 Liu Yaming], 2014, [地学前缘, Earth Science Frontiers], V21, P134

[20] Development of Antisense Oligonucleotide (ASO) Technology Against Tgf-β Signaling to Prevent Scarring During Flexor Tendon Repair [J].

Loiselle, Alayna E. ;

Yukata, Kiminori ;

Geary, Michael B. ;

Kondabolu, Sirish ;

Shi, Shanshan ;

Jonason, Jennifer H. ;

Awad, Hani A. ;

O'Keefe, Regis J. .

JOURNAL OF ORTHOPAEDIC RESEARCH, 2015, 33 (06) :859-866

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