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Publication : Establishment of a Murine Pro-acinar Cell Line to Characterize Roles for FGF2 and α3β1 Integrins in Regulating Pro-acinar Characteristics.

First Author  Thiemann RF Year  2019
Journal  Sci Rep Volume  9
Issue  1 Pages  10984
PubMed ID  31358811 Mgi Jnum  J:286696
Mgi Id  MGI:6388256 Doi  10.1038/s41598-019-47387-y
Citation  Thiemann RF, et al. (2019) Establishment of a Murine Pro-acinar Cell Line to Characterize Roles for FGF2 and alpha3beta1 Integrins in Regulating Pro-acinar Characteristics. Sci Rep 9(1):10984
abstractText  Radiation therapy for head and neck cancers results in permanent damage to the saliva producing acinar compartment of the salivary gland. To date, a pure pro-acinar cell line to study underlying mechanisms of acinar cell differentiation in culture has not been described. Here, we report the establishment of a pro-acinar (mSG-PAC1) and ductal (mSG-DUC1) cell line, from the murine submandibular salivary gland (SMG), which recapitulate developmental milestones in differentiation. mSG-DUC1 cells express the ductal markers, keratin-7 and keratin-19, and form lumenized spheroids. mSG-PAC1 cells express the pro-acinar markers SOX10 and aquaporin-5. Using the mSG-PAC1 cell line, we demonstrate that FGF2 regulates specific steps during acinar cell maturation. FGF2 up-regulates aquaporin-5 and the expression of the alpha3 and alpha6 subunits of the alpha3beta1 and alpha6beta1 integrins that are known to promote SMG morphogenesis and differentiation. mSG-DUC1 and mSG-PAC1 cells were derived from genetically modified mice, homozygous for floxed alleles of the integrin alpha3 subunit. Similar to SMGs from alpha3-null mice, deletion of alpha3 alleles in mSG-PAC1 cells results in the up-regulation of E-cadherin and the down-regulation of CDC42. Our data indicate that mSG-DUC1 and mSG-PAC1 cells will serve as important tools to gain mechanistic insight into salivary gland morphogenesis and differentiation.
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