Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil.
Mol Cell Endocrinol. 2018 Dec 5;477:39-47. doi: 10.1016/j.mce.2018.05.013. Epub 2018 May 21.
The success of islet transplantation has improved lately. Unfortunately, it is still compromised by cell loss. We have shown that prolactin (PRL) inhibits beta-cell apoptosis and up-regulates the antiapoptotic Heat Shock Protein B1 (HSPB1) in human islets. Since its function in pancreatic islets has not been studied, we explored the role of HSPB1 in PRL-induced beta-cell survival. The significant PRL-induced cytoprotection in control cells was abrogated in HSPB1 silenced cells, overexpression of HSPB1 recovered survival. PRL-mediated inhibition of cytokine-induced caspase activities and cytokine-induced decrease of BCL-2/BAX ratio was significantly reverted in knocked-down cells. Kinetics of HSPB1 and HSF1 expression were studied in primary cultures of murine and human pancreatic islets. These findings are highly relevant for the improvement of clinical islet transplantation success rate since our results demonstrated a key role for HSPB1 pointing it as a promising target for beta-cell cytoprotection through the up-regulation of an endogenous protective pathway.
胰岛移植的成功率最近有所提高。不幸的是，它仍然受到细胞损失的影响。我们已经表明，催乳素（PRL）抑制β细胞凋亡，并上调人胰岛中的抗凋亡热休克蛋白 B1（HSPB1）。由于其在胰腺胰岛中的功能尚未研究，我们探讨了 HSPB1 在 PRL 诱导的β细胞存活中的作用。在沉默 HSPB1 的细胞中，PRL 诱导的细胞保护作用被消除，而过表达 HSPB1 恢复了存活。在敲低细胞中，PRL 介导的细胞因子诱导的半胱天冬酶活性抑制和细胞因子诱导的 BCL-2/BAX 比值下降明显逆转。在原代培养的鼠和人胰岛中研究了 HSPB1 和 HSF1 的表达动力学。这些发现对于提高临床胰岛移植成功率具有重要意义，因为我们的结果表明 HSPB1 具有关键作用，指出它作为通过上调内源性保护途径保护β细胞的有希望的靶标。
