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

Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation

“…Our observations showed that in contrast to the controls, where endocrine progenitor cells migrated and aggregated outside of ductal cords, the mGFP + cells in Itgb1 ΔEndo/ΔEndo explants readily aggregated before moving away from the cords ( Figure 2—figure supplement 1D , white arrows). In contrast to our findings, previous studies using Ins-Cre or RIP-Cre to ablate Itgb1 after endocrine progenitors have differentiated into insulin-producing cells did not report any observable islet aggregation or migration defects ( Diaferia et al, 2013 ; Win et al, 2020 ). However, Ngn3-Cre -mediated Itgb1 deletion would occur much earlier in embryonic stages ( Figure 1A ), suggesting that Itgb1 signaling regulates the migration and aggregation of progenitor cells in the endocrine lineage during the islet developmental process.…”

“…Both Itgb1 ΔEndo/ΔEndo and Itgb1 Δ Matureβ/ Δ Matureβ mice demonstrate reduced vascularization, highlighting the importance of ECM signaling in vascular interactions throughout stages from embryonic endocrine cells to mature β-cells. This aligns with previous research using MIP-Cre to create Itgb1 -knockout mice, which also exhibited decreased islet vascularization ( Win et al, 2020 ). The critical role of Itgb1 signaling in organ vascularization seems universal; studies indicate that Itgb1 inactivation in pituitary endocrine epithelial cells and kidney cells leads to a loss of vasculature ( Mohamed et al, 2020 ; Scully et al, 2016 ).…”

Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation

“…As both Itgb1 ΔEndo/ΔEndo and Itgb1 Δ Matureβ/ Δ Matureβ mice show reduced vascularization, the involvement of ECM signaling in vascular interactions is critical in both embryonic endocrine cells and mature β-cells. This concurs with the study using MIP-Cre to generate Itgb1 -knockout mice, which showed reduced islet vascularization (Win et al, 2020). The involvement of Itgb1 signaling in organ vascularization appears to be a universal requirement: as shown in pituitary endocrine epithelial cells and kidney cells, Itgb1-inactivation leads to vasculature loss (Mohamed et al, 2020; Scully et al, 2016).…”

“…ECM signaling activation to regulate endocrine cell migration appears to be required only in early developmental stages, as the Itgb1 Δ Matureβ/ Δ Matureβ islets do not show migration defects. This is also supported by other studies using Ins-Cre or RIP-Cre to ablate Itgb1 after endocrine progenitors have already differentiated into insulin-producing cells, as those studies do not report observable migration defects (Diaferia et al, 2013; Win et al, 2020). This suggests that ECM-Integrin signaling are critical for endocrine cell migration, and that the time window for endocrine cell initiation is small.…”

Urinary protein changes during the short-term growth and development of rats

“…In addition, NDRG1 (N-myc downstream-regulated gene 1 protein) is an intracellular protein that can be induced under a variety of stress and cell growth regulatory conditions, and NDRG1 is upregulated by cell differentiation signals and inhibits tumor metastasis in various cancer cell lines [ 21 ]. Win PW et al showed that β1 integrin beta signaling is required to maintain islet mass and angiogenesis during specific transition windows in developing β-cells [ 22 ], while Masuzaki R et al investigated integrin β1 as a key determinant of liver structure and played a key role as a modulator of TGF-β secretion [ 23 ]. A review by Barzegar Behrooz A et al reveals that CD133 (prominin-1) may increase angiogenesis and promote the growth and differentiation of neural cells by activating the Wnt signaling pathway [ 24 ].…”