VDAC2 Mediates the Apoptosis of Cashmere Goat Hair Follicle Stem Cells Through the P53 Signaling Pathway

TL;DR

The study shows that VDAC2 causes apoptosis in cashmere goat hair follicle stem cells through the P53 signaling pathway, affecting hair growth cycles.

Contribution

This study identifies VDAC2 as a key regulator of apoptosis in cashmere goat secondary hair follicle stem cells via the P53 pathway.

Findings

VDAC2 is differentially expressed in hair follicles during growth, senescence, and resting phases.

VDAC2 overexpression promotes apoptosis in secondary hair follicle stem cells.

The P53 signaling pathway is activated by VDAC2 and contributes to stem cell apoptosis.

Abstract

Apoptosis regulates tissue homeostasis by removing unwanted or damaged cells during development and aging. Apoptosis plays a key role in the cyclic cycle of the hair follicle by removing a portion of the hair follicle cells through apoptotic mechanisms to prepare the follicle for the next growth cycle. VDAC2, located in the outer mitochondrial membrane, is a key apoptosis regulator, but its role in the hair follicle of cashmere goats remains unclear. We found by proteome sequencing that VDAC2 was significantly differentially expressed in the hair follicle of the Albas cashmere goat during the growth, senescence, and resting phases. RNA-seq analysis indicated that VDAC2 affected the growth of secondary hair follicle stem cells through the P53 signaling pathway. In addition, overexpression of VDAC2 followed by a P53 inhibitor partially alleviated VDAC2-induced apoptosis. These results suggest that VDAC2 plays an important role in secondary hair follicle stem cell apoptosis.

Hair follicle stem cells (HFSCs) are pluripotent stem cells located in the bulges of hair follicles. Apoptosis regulates tissue homeostasis by eliminating unnecessary or damaged cells during development and aging. VDAC2, located in the outer mitochondrial membrane (MOM), is a key apoptosis regulator, but its role in cashmere goat hair follicles remains unclear. In previous studies, through proteomic sequencing, we found that VDAC2 was significantly differentially expressed in the anagen, catagen, and telogen phases of the hair follicles of Albas cashmere goats. This study aimed to explore the role of VDAC2 in secondary hair follicle stem cells (SHFSCs) and preliminarily investigate its regulatory mechanism through RNA-seq. Overexpression of VDAC2 promoted apoptosis in SHFSCs, while knockdown had the opposite effect. RNA-seq analysis, together with expression validation of downstream genes, indicates that the P53 signaling pathway may be involved in VDAC2-mediated SHFSC regulation. RT-qPCR and Western blotting confirmed that VDAC2 activated the P53 signaling pathway in SHFSCs. Furthermore, the use of a P53 inhibitor after VDAC2 overexpression partially rescued the apoptosis of cells caused by VDAC2. These results demonstrate that VDAC2 plays an important role in SHFSC apoptosis. Our findings greatly enhance our understanding of the role of VDAC2 in SHFSC apoptosis and hair follicle growth.

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