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Sex difference on fibroblast growth factors (FGFs) expression in skin and wound of streptozotocin(STZ)-induced type 1 diabetic mice

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Abstract

Background

Fibroblast growth factors (FGFs) are key factors affecting diabetic wound healing. However, the FGF family’s expression patterns in skin and wounds influenced by both diabetes and sex are still unknown.

Methods and results

In this study, normal and Streptozotocin (STZ)-induced type 1 diabetic C57BL/6J male and female mice were used to study the FGF family’s expression in non-wound skin and wounds. We found that the expression patterns of Fgfs were affected by sex in both normal and diabetic animals during wound healing. In normal control mice, sex difference had a limited effect on basal skin Fgf expressions. However, it significantly influenced Fgf expressions in wounds. Type 1 diabetes reduced basal and wound-induced skin Fgf expressions. Female mice had far lower wound-induced skin Fgf expressions in diabetic mice. In addition, sex differently influenced Fibroblast growth factors receptor (Fgfr) expression patterns of non-wound skin and wounds in both normal and diabetic mice. Moreover, female mice had a lower relative level of Fibronectin leucine-rich repeat transmembrane protein 2 (FLRT2) — a FGFR activation marker gene — in wound and blood plasma. Correspondingly, the wound areas of female animals were larger than that of male animals in the early stage of wound healing (less than 3-day injury).

Conclusion

Our research shows that the FGF family have different expression patterns in normal and diabetic wound healing in mice of different sex. Additionally, we also provide the signatures of individual FGFs in diabetic wound healing, which deserve further investigation.

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Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

Abbreviations

FGFs:

fibroblast growth factors

FGFR:

fibroblast growth factor receptor

FLRT:

fibronectin-leucine-rich transmembrane

GTEx:

Genotype-Tissue Expression

HRP:

Horseradish Peroxidase

OD:

Optical Density

STZ:

Streptozotocin

TBP:

TATA-box binding protein

T1D:

type 1 diabetes.

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Acknowledgements

This work was supported by Beijing Municipal Natural Science Foundation (7222119), the CAMS Innovation Fund (2021-1-I2M-029, 2016-I2M-3-007), the China’s National Key R&D Programs (2017YFE0112900, 2018ZX09711001-003-005), and the NSFC (82070877, 81770847, and 81470159).

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Authors and Affiliations

  1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica of Peking Union Medical College, Jia 2nd, Nanwei Road, Xicheng district, 100050, Beijing, P.R. China

    Nuo-qi Wang, Wei-hua Jia, Lin Yin, Na Li, Mei-dai Liang, Jia-min Shang, Bi-yu Hou, Li Zhang, Gui-fen Qiang, Guan-hua Du & Xiu-ying Yang

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  1. Nuo-qi Wang
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Contributions

DGH, YXY and QGF contributed to the study conception and design. WNQ, JWH, YL, LMD and SJM contributed to the acquisition of data. HBY, LZ and WNQ contributed to the analysis of data. WNQ and YXY wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Guan-hua Du or Xiu-ying Yang.

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The authors have no relevant financial or non-financial interests to disclose.

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All the animal experimental procedures were in compliance with the guidelines and granted by the Animal Care and Use Committee (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College).

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Wang, Nq., Jia, Wh., Yin, L. et al. Sex difference on fibroblast growth factors (FGFs) expression in skin and wound of streptozotocin(STZ)-induced type 1 diabetic mice. Mol Biol Rep 50, 1981–1991 (2023). https://doi.org/10.1007/s11033-022-08094-6

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