Lnc-PFAR facilitates autophagy and exacerbates pancreatic fibrosis by reducing pre-miR-141 maturation in chronic pancreatitis.
Lnc-PFAR facilitates autophagy and exacerbates pancreatic fibrosis by reducing pre-miR-141 maturation in chronic pancreatitis.
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Lnc-PFAR 通过减少慢性胰腺炎中的 pre-miR-141 成熟来促进自噬并加剧胰腺纤维化
DOI：
10.1038/s41419-021-04236-z
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发表时间：
2021-10-25
影响因子：
9
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Zhang T;Zhang G;Yang W;Chen H;Hu J;Zhao Z;Cheng C;Li G;Xie Y;Li Y;Kong R;Wang Y;Wang G;Chen H;Bai XW;Pan S;Sun B;Li L
慢性胰腺炎（chronic pancreatitis，CP）是一种进行性胰腺炎性纤维化，伴有不可逆的内分泌和外分泌功能障碍的疾病。胰腺星状细胞（Pancreatic stellate cells，PSC）广泛分布于胰腺基质中，PSC活化已被证明是胰腺纤维化的主要原因之一。我们先前的研究表明，自噬在CP组织中被显著激活，这有助于PSC激活和胰腺纤维化。长链非编码RNA（LncRNA）已被认为是纤维化相关疾病的关键调节因子。LncRNA与RNA结合蛋白相互作用或构建竞争性内源性RNA（ceRNA）假说，从而引发纤维化过程。到目前为止，lncRNA对PSC活化和胰腺纤维化的影响尚未明确研究。在本研究中，发现一种新的lncRNA命名为Lnc-PFAR在小鼠和人CP组织中高度表达。我们的数据显示，Lnc-PFAR通过RB 1CC 1诱导的自噬促进PSC活化和胰腺纤维化。Lnc-PFAR通过抑制miR-141前体成熟来降低miR-141的表达，最终上调RB 1CC 1和纤维化相关指标的表达。同时，Lnc-PFAR通过触发自噬，增强PSC的活化和胰腺纤维化。我们的研究探讨了一种新的lncRNA诱导的机制，促进胰腺纤维化的发展，Lnc-PFAR被认为是一个有前景的治疗目标，在临床情况下。
Chronic pancreatitis (CP) is described as progressive inflammatory fibrosis of pancreas, accompanied with irreversible impaired endocrine and exocrine insufficiency. Pancreatic stellate cells (PSCs) are widely distributed in the stroma of the pancreas and PSCs activation has been shown as one of the leading causes for pancreatic fibrosis. Our previous study has revealed that autophagy is dramatically activated in CP tissues, which facilitates PSCs activation and pancreatic fibrosis. Long non-coding RNAs (LncRNAs) have been recognized as crucial regulators for fibrosis-related diseases. LncRNAs interact with RNA binding protein or construct competitive endogenous RNA (ceRNA) hypothesis which elicited the fibrotic processes. Until now, the effects of lncRNAs on PSCs activation and pancreatic fibrosis have not been clearly explored. In this study, a novel lncRNA named Lnc-PFAR was found highly expressed in mouse and human CP tissues. Our data revealed that Lnc-PFAR facilitates PSCs activation and pancreatic fibrosis via RB1CC1-induced autophagy. Lnc-PFAR reduces miR-141 expression by suppressing pre-miR-141 maturation, which eventually upregulates the RB1CC1 and fibrosis-related indicators expression. Meanwhile, Lnc-PFAR enhanced PSCs activation and pancreatic fibrosis through trigging autophagy. Our study interrogates a novel lncRNA-induced mechanism in promoting the development of pancreatic fibrosis, and Lnc-PFAR is suggested to be a prospective therapeutic target in clinical scenarios.
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作者：
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通讯作者：
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