Qiuni Gao,Shangyu Zeng,Yupeng Chen,Ying Bao,Haiyan Cui
Alopecia, a prevalent condition driven by abnormal hair follicle cycling and stem cell (HFSCs) dysregulation, underscores the need to elucidate molecular mechanisms governing HFSCs activation. While the nuclear factor of activated T cells c1 (NFATc1) is known to maintain HFSCs quiescence by suppressing cyclin-dependent kinase 4 (CDK4), the upstream regulators of this pathway remain unclear. Here, we identify MafB as a key modulator of HFSCs dynamics through NFATc1 signaling. Transcriptome sequencing of murine skin revealed elevated MafB expression during active hair regeneration. Adenoviral overexpression of MafB in depilated mice accelerated hair regrowth, increased hair follicle diameter, and enhanced HFSCs proliferation. Conversely, MafB knockdown suppressed regeneration and reduced the prolifiration ability of HFSCs. In vitro , MafB overexpression promoted HFSCs proliferation, migration, and differentiation, while mechanistic studies demonstrated MafB inhibits NFATc1 transcription, thereby relieving CDK4 repression and activating Wnt/β-catenin signaling. Rescue experiments confirmed NFATc1 restoration abrogated MafB-induced HFSCs activation. These findings establish MafB as a critical regulator of hair follicle cycling through the NFATc1/CDK4 axis, offering novel therapeutic avenues for alopecia.
Purpose This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR). Patients and Methods Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 μg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×10 7 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 μg OVA from day 21 to 27. Results The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4 + T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity. Conclusion MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.
Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia with osteolysis at the carpal and tarsal bones. Heterozygous missense mutations in the transcription factor MAFB are found in patients with MCTO. MAFB is reported to negatively regulate osteoclastogenesis in vitro. However, the in vivo function of MAFB and its relation to MCTO remains unknown. In this study, we generated zebrafish MAFB homologmafbbmutant utilizing CRISPR/Cas9 technology.Mafbbdeficient zebrafish demonstrated enhanced osteoclast cell differentiation and abnormal cartilage and bone development resembling MCTO patients. It is known that osteoclasts are hematopoietic cells derived from macrophages. Loss ofmafbbcaused selective expansion of definitive macrophages and myeloid cells, supporting thatmafbbrestricts myeloid differentiation in vivo. We also demonstrate that MAFB MCTO mutations failed to rescue the defective osteoclastogenesis inmafbb−/−embryos, but did not affect osteoclast cells in wild type embryos. The mechanism of MCTO mutations is likely haploinsufficiency. Zebrafishmafbbmutant provides a useful model to study the function of MAFB in osteoclastogenesis and the related MCTO disease.Keywords:MAFB;Multicentric Carpotarsal Osteolysis (MCTO);osteoclasts;macrophage and monocytes;zebrafish
危险品化学品经营许可证（带存储）