TRIM9 regulates the proliferation and apoptosis of dermal papilla cells by activating the Wnt/β-catenin signaling pathway to improve androgenetic alopecia.

BACKGROUND AND PURPOSE: Dermal papilla cells (DPCs) are signaling hubs for hair follicle growth and play a critical role in hair growth in patients with androgenetic alopecia (AGA). TRIM9, a tripartite motif (TRIM)-family E3 ubiquitin ligase, regulates cell differentiation, proliferation, and apoptosis. This study aimed to investigate the effects of TRIM9 on the proliferation and apoptosis of DPCs.

METHODS

AGA mouse and cellular models were induced by dihydrotestosterone (DHT) treatment to conduct experimental investigations. The damage to human dermal papilla cells (hDPCs) and mouse dorsal skin tissues was assessed using CCK-8 assay, flow cytometry, hematoxylin and eosin (HE) staining, and TUNEL staining. The expression levels of relevant genes and proteins were detected by real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Co-immunoprecipitation (Co-IP) assays were performed to examine the interactions of β-TrCP with TRIM9 and β-Catenin, as well as the ubiquitination level of β-Catenin.

RESULTS

This study revealed that TRIM9 expression is downregulated in AGA. Overexpression of TRIM9 can improve hair growth in AGA mice, promote the proliferation of hDPCs in vitro, and inhibit apoptosis. In terms of regulatory mechanisms, β-catenin is also downregulated in AGA. The overexpression of TRIM9 promoted the expression of β-catenin, whereas the addition of the Wnt/β-catenin signaling pathway inhibitor XAV939 partially attenuated the effects of TRIM9 overexpression, inhibited hDPCs proliferation and promoted apoptosis. Further coimmunoprecipitation experiments revealed that β-catenin is a ubiquitination substrate of β-TrCP. TRIM9 can bind competitively to β-TrCP, thereby inhibiting β-TrCP-mediated ubiquitination and degradation of β-catenin.

CONCLUSION

TRIM9 competitively binds to β-TrCP, inhibiting β-TrCP-mediated ubiquitination and degradation of β-catenin, activating the Wnt/β-catenin signaling pathway, promoting hDPCs proliferation, suppressing apoptosis, and ultimately ameliorating AGA progression.