چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| Porcupine (Porcn) enzyme plays an essential role in Wnt signaling activation. Stearoyl-CoA desaturase-1 (SCD1) is required to provide Porcn substrates. The aim of this study was to determine the effect of a novel Porcn inhibitor on the fate of human embryonic stem cells (hESCs) and the reliance of Porcn on SCD1 activity. hESCs were cultured on a feeder layer or Matrigel-coated plates. Small molecules WNT974 (LGK-974) and CAY10566 were used to inhibit Porcn and SCD1 activity, respectively. We assessed the effect of Porcn inhibition on viability, expression of Wnt signaling targets, pluripotency markers, proliferation, differentiation, and protein fatty acylation. hESCs' conditioned medium (CM) containing secreted Wnt proteins were applied in rescue experiments. To examine the catalytic dependency of Porcn on SCD1, the results of combined inhibitor treatment were compared with the SCD1 inhibitor alone. LGK-974 at the selected concentrations showed mild effects on hESCs viability, but significantly reduced messenger RNA and protein expression of Wnt signaling targets (Axin-2 and c-Myc) and pluripotency markers (OCT-4 and SOX-2) (p < .05). Adding 1 μM of Porcn inhibitor reduced proliferation (p = .03) and enhanced differentiation capacity into ectodermal progenitors (p = .02), which were reverted by CM. Click chemistry reaction did not show significant alteration in protein fatty acylation upon LGK-974 treatment. Moreover, combined inhibitor treatment caused no further substantial reduction in Wnt signaling targets, pluripotency markers, and protein fatty acylation relative to CAY10566-treated cultures. The substrate availability for Porcn activity is regulated by SCD1 and targeting Porcn by LGK-974 prompts the transition of hESCs from self-renewal state to ectodermal lineage. |
| نویسنده | نفر چندم مقاله |
|---|---|
| اشکان کلانتری چروده | اول |
| سید وحید حسینی | دوم |
| امیر مهدی زاده حقیقی | سوم |
| سعید نظری سلطان احمد | چهارم |
| رضا رهبرقاضی | پنجم |
| حجت اله نوزاد چروده | ششم |
| محمد نوری | هفتم |
| مسعود دارابی امین | هشتم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| 2022 Cell Biochemistry Function KalantaryCharvadeh The porcupine inhibitor.pdf | 1401/04/04 | 2371863 | دانلود |
