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All-trans retinoic acid modulates proliferation and apoptosis of secondary hair follicle–dermal papilla cells in cashmere goats via the TGF-β2/Smad2/3 pathway

ABSTRACT: Cashmere, a fiber of high economic value, is produced by secondary hair follicles (SHFs), whose growth depends on the proliferation and apoptosis of SHF-derived dermal papilla cells (SHF-DPCs). All-trans retinoic acid (ATRA), a metabolite of vita min A, has shown inconsistent effects on hair follicle biology, with reports of both inhibition and stimulation. To clarify the role of ATRA in follicular development, we investigated its effects on the proliferation and apoptosis of in vitro–cultured SHF-DPCs isolated from Capra hircus (Albas cashmere goats). SHF-DPCs were obtained from scapular skin, and the optimal ATRA concentration (10−4 M) and treatment duration (24 h) were identified using Cell Counting Kit-8, 5-ethynyl-2′ deoxyuridine, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Cells were then assigned to an ATRA-treated group (10−4 M) or a control group. Proliferation, apoptosis, and cell cycle progression were evaluated, fol lowed by transcriptome sequencing. Transcriptomic analysis indicated enrich ment of the transforming growth factor-β (TGF-β) signaling pathway. Therefore, mRNA and protein levels of TGF-β2—a follicle growth–related regulator—and Smad2/3 phosphorylation were examined. The TGF-β type I/II receptor inhibitor LY2109761 was used to further validate the involvement of this pathway. ATRA inhibited SHF-DPC proliferation by inducing G1-phase cell cycle arrest and pro moted apoptosis by upregulating Bax expression while downregulating Bcl-2 protein expression. Transcriptomic analysis showed that ATRA upregulated TGFβ2 expression in SHF-DPCs. Gene Ontology analysis revealed enrichment of genes related to proliferation and apoptosis, such as “cell migration” and “cell cycle.” Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the TGF β signaling pathway as a major regulatory target. Treatment with LY2109761 par tially reversed ATRA-induced reductions in proliferation, increases in apoptosis, and elevations in Smad2/3 phosphorylation. Overall, ATRA inhibits proliferation and promotes apoptosis in SHF-DPCs, likely through the TGF-β2/Smad2/3 path way. These findings provide novel insights into ATRA-mediated regulation of hair growth and offer a theoretical basis for future research on cashmere goat SHF development.

ORGANISM(S): Capra hircus

PROVIDER: GSE324826 | GEO | 2026/04/08

REPOSITORIES: GEO

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Project description:Inner Mongolia Cashmere Goat is a local excellent breed of cashmere and meat dual-purpose, which is a typical heterogeneous indumentum. The hair follicles cycle through periods of vigorous growth (anagen), a regression caused by apoptosis (catagen), and relative rest (telogen). At present, it is not clear which genes affect the cycle transformation of hair follicles and unclear how proteins impact the creation and expansion of hair follicles. In this work, we investigated the possible pathways of transformation and apoptosis in goat hair follicles using multi-omics joint analysis methodologies. The results showed that 917 , 1187 and 716 proteins were specifically expressed in anagen, catagen and telogen. The result of gene ontology (GO) annotation showed that differentially expressed proteins（DEPs) are in different growth cycle periods, and enriched GO items are mostly related to the transformation of cells and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment result indicated that the apoptosis process has a great impact on hair follicle's growth cycle. The results of the protein interaction network of differential proteins showed that the Ribosomal Protein family ( RPL4, RPL8, RPS16, RPS18, RPS2, RPS27A, RPS3 ) was the core protein in the network. The results of combined transcriptome and proteomics analysis showed that there were 16,34, and 26 overlapped DEGs and DEPs in the comparison of anagen VS catagen, catagen VS telogen and anagen VS telogen, of which API5 plays an important role in regulating protein and gene expression levels. We focused on API5 and Ribosomal protein and found that API5 affected the apoptosis process of hair follicles, and Ribosomal Protein was highly expressed in the resting stage of hair follicles. They are both useful as molecular marker candidate genes to study hair follicle growth and apoptosis, and they both have an essential function in the cycle transition process of hair follicles. The results of this study may provide a theoretical basis for further research on the growth and development of hair follicles in Inner Mongolian Cashmere goats.

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All-trans retinoic acid modulates proliferation and apoptosis of secondary hair follicle–dermal papilla cells in cashmere goats via the TGF-β2/Smad2/3 pathway

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