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首页> 外文期刊>Molecular biology of the cell >Autocrine Transforming Growth Factor-β1 Activation Mediated by Integrin αVβ3 Regulates Transcriptional Expression of Laminin-332 in Madin-Darby Canine Kidney Epithelial Cells
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Autocrine Transforming Growth Factor-β1 Activation Mediated by Integrin αVβ3 Regulates Transcriptional Expression of Laminin-332 in Madin-Darby Canine Kidney Epithelial Cells

机译：整联蛋白αVβ3介导的自分泌转化生长因子-β1激活调节Ladyin-332在麦丁-达比犬肾上皮细胞中的转录表达。

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摘要

Laminin (LM)-332 is an extracellular matrix protein that plays a structural role in normal tissues and is also important in facilitating recovery of epithelia from injury. We have shown that expression of LM-332 is up-regulated during renal epithelial regeneration after ischemic injury, but the molecular signals that control expression are unknown. Here, we demonstrate that in Madin-Darby canine kidney (MDCK) epithelial cells LM-332 expression occurs only in subconfluent cultures and is turned-off after a polarized epithelium has formed. Addition of active transforming growth factor (TGF)-β1 to confluent MDCK monolayers is sufficient to induce transcription of the LM α3 gene and LM-332 protein expression via the TGF-β type I receptor (TβR-I) and the Smad2–Smad4 complex. Significantly, we show that expression of LM-332 in MDCK cells is an autocrine response to endogenous TGF-β1 secretion and activation mediated by integrin αVβ3 because neutralizing antibodies block LM-332 production in subconfluent cells. In confluent cells, latent TGF-β1 is secreted apically, whereas TβR-I and integrin αVβ3 are localized basolaterally. Disruption of the epithelial barrier by mechanical injury activates TGF-β1, leading to LM-332 expression. Together, our data suggest a novel mechanism for triggering the production of LM-332 after epithelial injury.
机译：层粘连蛋白（LM）-332是一种细胞外基质蛋白，在正常组织中起结构作用，并且在促进上​​皮从损伤中恢复中也很重要。我们已经表明，LM-332的表达在缺血性损伤后的肾上皮再生过程中被上调，但是控制该表达的分子信号尚不清楚。在这里，我们证明了在Madin-Darby犬肾（MDCK）上皮细胞中LM-332表达仅在亚汇合培养物中发生，并且在极化的上皮细胞形成后被关闭。在融合的MDCK单层中添加活性转化生长因子（TGF）-β1足以通过TGF-βI型受体（TβR-I）和Smad2-Smad4复合体诱导LMα3基因的转录和LM-332蛋白的表达。 。重要的是，我们表明，MDCK细胞中LM-332的表达是对整联蛋白αVβ3介导的内源性TGF-β1分泌和激活的自分泌反应，因为中和抗体会阻止亚融合细胞中LM-332的产生。在汇合的细胞中，潜在的TGF-β1顶端分泌，而TβR-1和整联蛋白αVβ3定位在基底外侧。机械损伤破坏上皮屏障可激活TGF-β1，从而导致LM-332表达。总之，我们的数据提示了上皮损伤后触发LM-332产生的新机制。

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