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Beta-cell β1 integrin deficiency affects in utero development of islet growth and vascularization

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Abstract

The β1 integrin subunit contributes to pancreatic beta cell growth and function through communication with the extracellular matrix (ECM). The effects of in vitro and in vivo β1 integrin knockout have been extensively studied in mature islets, yet no study to date has examined how the loss of β1 integrin during specific stages of pancreatic development impacts beta cell maturation. Beta-cell-specific tamoxifen-inducible Cre recombinase (MIP-CreERT) mice were crossed with mice containing floxed Itgb1 (β1 integrin) to create an inducible mouse model (MIPβ1KO) at the second transition stage (e13.5) of pancreas development. By e19.5–20.5, the expression of beta-cell β1 integrin in fetal MIPβ1KO mice was significantly reduced and these mice displayed decreased beta cell mass, density and proliferation. Morphologically, fetal MIPβ1KO pancreata exhibited reduced islet vascularization and nascent endocrine cells in the ductal region. In addition, decreased ERK phosphorylation was observed in fetal MIPβ1KO pancreata. The expression of transcription factors needed for beta-cell development was unchanged in fetal MIPβ1KO pancreata. The findings from this study demonstrate that β1 integrin signaling is required during a transition-specific window in the developing beta-cell to maintain islet mass and vascularization.

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Acknowledgments

The authors would like to thank Dr. Louis Philipson from the University of Chicago, Chicago, IL, USA, for providing the MIP-CreER mouse model. We would also like to thank Mr. Jason Peart for his technical assistance.

Author contribution statement

PWW contributed to the organization and maintenance of the MIPβ1KO line, acquisition and interpretation of data and preparation of the submitted manuscript. AO contributed to the acquisition and interpretation of data and to manuscript preparation. JL contributed to technical assistance, acquisition of data and manuscript editing. RW contributed to the design of experiments within this project and preparation of the submitted manuscript.

Funding

This study was funded by the Natural Sciences & Engineering Research Council of Canada (grant no. RGPIN/04658-2017).

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Authors and Affiliations

  1. Children’s Health Research Institute, Victoria Research Laboratories, London, Ontario, N6C 2V5, Canada

    Phyo Wei Win, Amanda Oakie, Jinming Li & Rennian Wang

  2. Department of Physiology & Pharmacology, University of Western Ontario, London, Ontario, N6A 3K7, Canada

    Phyo Wei Win, Jinming Li & Rennian Wang

  3. Department of Pathology & Laboratory Medicine, University of Western Ontario, London, Ontario, N6A 3K7, Canada

    Amanda Oakie

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  1. Phyo Wei Win
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Correspondence to Rennian Wang.

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Win, P.W., Oakie, A., Li, J. et al. Beta-cell β1 integrin deficiency affects in utero development of islet growth and vascularization. Cell Tissue Res 381, 163–175 (2020). https://doi.org/10.1007/s00441-020-03179-9

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  • DOI: https://doi.org/10.1007/s00441-020-03179-9

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