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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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Expression dynamics of GPR39 after wounding.(a) Whole-mount LacZ staining in wounded skin of Gpr39+/lacZ mice on different days after wounding. Inserted in the D4 image is a negative control showing no LacZ staining in Gpr39+/+ mice. (b) Microscopic observation of lacZ expression in wounded skin of Gpr39+/lacZ mice on different days after wounding. The upper panels are magnifications of the framed areas in the lower panels. (c) GPR39 immunostaining on D2, 4, 6 and 8 after wounding. The upper panels are magnifications of the framed areas in the lower panels. Black arrows indicate lacZ+ cells. Asterisks indicate the wound site. Epi, epidermis; HF, hair follicle. Bar = 50 μm.
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f3: Expression dynamics of GPR39 after wounding.(a) Whole-mount LacZ staining in wounded skin of Gpr39+/lacZ mice on different days after wounding. Inserted in the D4 image is a negative control showing no LacZ staining in Gpr39+/+ mice. (b) Microscopic observation of lacZ expression in wounded skin of Gpr39+/lacZ mice on different days after wounding. The upper panels are magnifications of the framed areas in the lower panels. (c) GPR39 immunostaining on D2, 4, 6 and 8 after wounding. The upper panels are magnifications of the framed areas in the lower panels. Black arrows indicate lacZ+ cells. Asterisks indicate the wound site. Epi, epidermis; HF, hair follicle. Bar = 50 μm.

Mentions: The expression pattern of GPR39 suggested that it might play a role in the skin. However, Gpr39−/− mice showed no obvious defects in skin development or homeostasis. Therefore, we created a skin wound environment to further explore the function of GPR39. After making 1/8-inch, circular, full-thickness cutaneous wounds in the backs of Gpr39+/lacZ mice (7- to 8-week-old), we noted that GPR39 had intriguing expression dynamics in the wound area. On D2 after wounding, lacZ signals were barely detected in the epidermis (Fig. 3 a, b; first column). However, by D4, lacZ signals became evident in the epidermis at the edge of the wound (Fig. 3 a, b; second column). Along with the healing, the epidermal lacZ signals became restricted to the area within the wound on D6 (Fig. 3 a, b; third column). Upon wound closure, LacZ staining in the epidermis had decreased (Fig. 3 a, b; last column). The expression of the GPR39 protein in the wounded epidermis from D2 to D8 was also confirmed by immunostaining (Fig. 3c).


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)

Expression dynamics of GPR39 after wounding.(a) Whole-mount LacZ staining in wounded skin of Gpr39+/lacZ mice on different days after wounding. Inserted in the D4 image is a negative control showing no LacZ staining in Gpr39+/+ mice. (b) Microscopic observation of lacZ expression in wounded skin of Gpr39+/lacZ mice on different days after wounding. The upper panels are magnifications of the framed areas in the lower panels. (c) GPR39 immunostaining on D2, 4, 6 and 8 after wounding. The upper panels are magnifications of the framed areas in the lower panels. Black arrows indicate lacZ+ cells. Asterisks indicate the wound site. Epi, epidermis; HF, hair follicle. Bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300488&req=5

f3: Expression dynamics of GPR39 after wounding.(a) Whole-mount LacZ staining in wounded skin of Gpr39+/lacZ mice on different days after wounding. Inserted in the D4 image is a negative control showing no LacZ staining in Gpr39+/+ mice. (b) Microscopic observation of lacZ expression in wounded skin of Gpr39+/lacZ mice on different days after wounding. The upper panels are magnifications of the framed areas in the lower panels. (c) GPR39 immunostaining on D2, 4, 6 and 8 after wounding. The upper panels are magnifications of the framed areas in the lower panels. Black arrows indicate lacZ+ cells. Asterisks indicate the wound site. Epi, epidermis; HF, hair follicle. Bar = 50 μm.
Mentions: The expression pattern of GPR39 suggested that it might play a role in the skin. However, Gpr39−/− mice showed no obvious defects in skin development or homeostasis. Therefore, we created a skin wound environment to further explore the function of GPR39. After making 1/8-inch, circular, full-thickness cutaneous wounds in the backs of Gpr39+/lacZ mice (7- to 8-week-old), we noted that GPR39 had intriguing expression dynamics in the wound area. On D2 after wounding, lacZ signals were barely detected in the epidermis (Fig. 3 a, b; first column). However, by D4, lacZ signals became evident in the epidermis at the edge of the wound (Fig. 3 a, b; second column). Along with the healing, the epidermal lacZ signals became restricted to the area within the wound on D6 (Fig. 3 a, b; third column). Upon wound closure, LacZ staining in the epidermis had decreased (Fig. 3 a, b; last column). The expression of the GPR39 protein in the wounded epidermis from D2 to D8 was also confirmed by immunostaining (Fig. 3c).

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