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GPR39 marks specific cells within the sebaceous gland and contributes to skin wound healing.

Zhao H, Qiao J, Zhang S, Zhang H, Lei X, Wang X, Deng Z, Ning L, Cao Y, Guo Y, Liu S, Duan E - Sci Rep (2015)

Bottom Line: Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1.Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage.The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.

ABSTRACT
G protein-coupled receptors (GPCRs) mediate multiple key biological processes in the body. The orphan receptor GPR39 has been reported to be involved in various pathophysiological events. However, the function of GPR39 in skin biology remains unknown. Using a genetically engineered mouse strain in which lacZ expression faithfully replaced endogenous Gpr39 expression, we discovered a unique expression pattern of Gpr39 in the sebaceous gland (SG). Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1. Further investigations showed that GPR39 was spatiotemporally expressed during skin wound repair. Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage. The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

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Promoter activity and mRNA expression of Gpr39 in the skin.(a) Microscopic observation of LacZ staining in tail skin of Gpr39+/lacZ (top) and Gpr39+/+ (bottom) mice. Arrows indicate lacZ signals at the openings of SGs. (b) Whole-mount LacZ staining of an isolated intact hair follicle (HF) (left) and an HF with the sebocytes removed (right). The tissues were counter-stained with ORO. (c) RT-PCR examination of Gpr39 and Actb (as an internal control) expression in separate epidermal compartments. NEG, negative control; POS, positive control. (d) RNA in situ hybridisation of Gpr39 in the SG. (e) LacZ staining in the dorsal skin of Gpr39+/lacZ mice on different postnatal days. HF, hair follicle; SG, sebaceous gland; Epi, epidermis; HS, hair shaft; P20, postnatal Day 20. Bar (a) = 100 μm, (b) = 20 μm, (d) = 25 μm, (e) = 20 μm.
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f1: Promoter activity and mRNA expression of Gpr39 in the skin.(a) Microscopic observation of LacZ staining in tail skin of Gpr39+/lacZ (top) and Gpr39+/+ (bottom) mice. Arrows indicate lacZ signals at the openings of SGs. (b) Whole-mount LacZ staining of an isolated intact hair follicle (HF) (left) and an HF with the sebocytes removed (right). The tissues were counter-stained with ORO. (c) RT-PCR examination of Gpr39 and Actb (as an internal control) expression in separate epidermal compartments. NEG, negative control; POS, positive control. (d) RNA in situ hybridisation of Gpr39 in the SG. (e) LacZ staining in the dorsal skin of Gpr39+/lacZ mice on different postnatal days. HF, hair follicle; SG, sebaceous gland; Epi, epidermis; HS, hair shaft; P20, postnatal Day 20. Bar (a) = 100 μm, (b) = 20 μm, (d) = 25 μm, (e) = 20 μm.

Mentions: Using a previously described mouse model in which targeted insertion of the lacZ reporter gene disrupted the Gpr39 locus, we monitored the expression of Gpr39 by staining with X-gal. As shown in Fig. 1a, LacZ staining of the tail skin in 20-day-old Gpr39+/lacZ mice indicated specific Gpr39 promoter activity at the openings of SGs (Fig. 1a, top). Gpr39+/+ skin from negative-control littermate mice showed no such staining (Fig. 1a, bottom). In a separated hair follicle, lacZ+ cell clusters were surrounded by sebocytes positive for Oil-Red-O (ORO) (Fig. 1b, left panel). After these sebocytes had been removed, the lacZ+ cell cluster was clearly observed attached to the isthmus of the HF (Fig. 1b, right panel). We performed RT-PCR to examine the mRNA expression of Gpr39 in various epidermal compartments. The separation of the epidermal compartments was verified by the expression of different markers in their corresponding compartments (Fig. S1). As indicated in Fig. 1c, Gpr39 expression was detected in the pilosebaceous unit rather than in the interfollicular epidermis (IFE) (Fig. 1c). RNA in situ hybridisation also confirmed the existence of Gpr39 mRNA within the SG opening (Fig. 1d). lacZ signals were also detected in the dorsal skin and exhibited a temporal upregulation around postnatal Day 24, when hair follicles entered a new anagen phase (Fig. 1e), indicating the cellular dynamics of Gpr39 expression during the hair cycle.


GPR39 marks specific cells within the sebaceous gland and contributes to skin wound healing.

Zhao H, Qiao J, Zhang S, Zhang H, Lei X, Wang X, Deng Z, Ning L, Cao Y, Guo Y, Liu S, Duan E - Sci Rep (2015)

Promoter activity and mRNA expression of Gpr39 in the skin.(a) Microscopic observation of LacZ staining in tail skin of Gpr39+/lacZ (top) and Gpr39+/+ (bottom) mice. Arrows indicate lacZ signals at the openings of SGs. (b) Whole-mount LacZ staining of an isolated intact hair follicle (HF) (left) and an HF with the sebocytes removed (right). The tissues were counter-stained with ORO. (c) RT-PCR examination of Gpr39 and Actb (as an internal control) expression in separate epidermal compartments. NEG, negative control; POS, positive control. (d) RNA in situ hybridisation of Gpr39 in the SG. (e) LacZ staining in the dorsal skin of Gpr39+/lacZ mice on different postnatal days. HF, hair follicle; SG, sebaceous gland; Epi, epidermis; HS, hair shaft; P20, postnatal Day 20. Bar (a) = 100 μm, (b) = 20 μm, (d) = 25 μm, (e) = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f1: Promoter activity and mRNA expression of Gpr39 in the skin.(a) Microscopic observation of LacZ staining in tail skin of Gpr39+/lacZ (top) and Gpr39+/+ (bottom) mice. Arrows indicate lacZ signals at the openings of SGs. (b) Whole-mount LacZ staining of an isolated intact hair follicle (HF) (left) and an HF with the sebocytes removed (right). The tissues were counter-stained with ORO. (c) RT-PCR examination of Gpr39 and Actb (as an internal control) expression in separate epidermal compartments. NEG, negative control; POS, positive control. (d) RNA in situ hybridisation of Gpr39 in the SG. (e) LacZ staining in the dorsal skin of Gpr39+/lacZ mice on different postnatal days. HF, hair follicle; SG, sebaceous gland; Epi, epidermis; HS, hair shaft; P20, postnatal Day 20. Bar (a) = 100 μm, (b) = 20 μm, (d) = 25 μm, (e) = 20 μm.
Mentions: Using a previously described mouse model in which targeted insertion of the lacZ reporter gene disrupted the Gpr39 locus, we monitored the expression of Gpr39 by staining with X-gal. As shown in Fig. 1a, LacZ staining of the tail skin in 20-day-old Gpr39+/lacZ mice indicated specific Gpr39 promoter activity at the openings of SGs (Fig. 1a, top). Gpr39+/+ skin from negative-control littermate mice showed no such staining (Fig. 1a, bottom). In a separated hair follicle, lacZ+ cell clusters were surrounded by sebocytes positive for Oil-Red-O (ORO) (Fig. 1b, left panel). After these sebocytes had been removed, the lacZ+ cell cluster was clearly observed attached to the isthmus of the HF (Fig. 1b, right panel). We performed RT-PCR to examine the mRNA expression of Gpr39 in various epidermal compartments. The separation of the epidermal compartments was verified by the expression of different markers in their corresponding compartments (Fig. S1). As indicated in Fig. 1c, Gpr39 expression was detected in the pilosebaceous unit rather than in the interfollicular epidermis (IFE) (Fig. 1c). RNA in situ hybridisation also confirmed the existence of Gpr39 mRNA within the SG opening (Fig. 1d). lacZ signals were also detected in the dorsal skin and exhibited a temporal upregulation around postnatal Day 24, when hair follicles entered a new anagen phase (Fig. 1e), indicating the cellular dynamics of Gpr39 expression during the hair cycle.

Bottom Line: Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1.Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage.The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.

ABSTRACT
G protein-coupled receptors (GPCRs) mediate multiple key biological processes in the body. The orphan receptor GPR39 has been reported to be involved in various pathophysiological events. However, the function of GPR39 in skin biology remains unknown. Using a genetically engineered mouse strain in which lacZ expression faithfully replaced endogenous Gpr39 expression, we discovered a unique expression pattern of Gpr39 in the sebaceous gland (SG). Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1. Further investigations showed that GPR39 was spatiotemporally expressed during skin wound repair. Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage. The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

Show MeSH
Related in: MedlinePlus