Biologie Cellulaire et Moléculaire

Abstrait

miR-148a Transcriptionally Regulated by ZEB1 Suppresses Dermal Papilla Cell Proliferation and Promotes Cell Apoptosis via FGF7/MAPK Axis

Bai-He Wang, Fan Wu, Jie Zhang, Sheng-Nan Wang, Yuan-Yuan Li

Background: Alopecia Areata (AA) is a hair follicle-specific autoimmune disease. Dermal Papilla (DP) cells play key roles in development and growth of hair follicles. MicroRNAs (miRNAs) are closely related to cell activities of DP cells. Herein, we probe the function of miR-148a in regulating cell activities of DP cells.

Methods: The mRNA and protein expressions were assessed using qRT-PCR and western blot. DP cell proliferation was assessed by MTT and EdU assays. In addition, cell apoptosis was evaluated using flow cytometer.Finally, dual luciferase reporter assay was carried out to verify the binding relationship between ZEB1, miR-148a and fibroblast growth factor 7 (FGF7).

Results: Compared with the normal tissues, miR-148a was upregulated in AA skin tissues, while FGF7 was lowly expressed. Function assays displayed that inhibition of miR-148a could promote DP cell proliferation and suppressed cell apoptosis, while miR-148a overexpression showed the opposite effects. FGF7 was identified as a target gene of miR-148a. We subsequently displayed that FGF7 overexpression accelerated DP cell proliferation and suppressed cell apoptosis, which were abolished by RWJ64809 (mitogen-activated protein kinase (MAPK) inhibitor) treatment.
Additionally, FGF7 silencing or RWJ64809 treatment abrogated the effects of miR-148a inhibition on cell activities of DP cells. Finally, it was turned out that ZEB1 transcriptionally inhibited miR-148a expression.

Conclusion: MiR-148a might have great potential as therapeutic target for AA, since miR-148a inhibition induced by ZEB1 facilitated DP cell proliferation and suppressed apoptosis during AA progression through activating MAPK signaling pathway by regulating FGF7 expression.