The non-canonical BMP signaling pathway plays an important role in club cell regeneration,STEM CELLS

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The non-canonical BMP signaling pathway plays an important role in club cell regeneration
STEM CELLS ( IF 4.0 ) Pub Date : 2019-12-06 , DOI: 10.1002/stem.3125
Md Shafiquzzaman _{1,

2,

3} , Soma Biswas ₁ , Ping Li ₁ , Yuji Mishina ₄ , Baojie Li _{1,

5} , Huijuan Liu _{1,

2}

Affiliation

The bronchiole is a major site for the development of several life‐threatening disorders, including chronic obstructive pulmonary disease and lung adenocarcinomas. The bronchiolar epithelium is composed of club cells and ciliated epithelial cells, with club cells serving as progenitor cells. Presently, the identity of the cells involved in regeneration of bronchiolar epithelium and the underlying mechanisms remain incompletely understood. Here, we show that Prrx1, a homeobox transcription factor, can mark club cells in adult mice during homeostasis and regeneration. We further show that the noncanonical signaling pathway of BMPs, BMPR1A‐Tak1‐p38MAPK, plays a critical role in club cell regeneration. Ablation of Bmpr1a, Tak1, or Mapk14 (encoding p38α) in Prrx1+ club cells caused minimal effect on bronchiolar epithelium homeostasis, yet it resulted in severe defects in club cell regeneration and bronchiole repair in adult mice. We further show that this pathway supports proliferation and expansion of the regenerating club cells. Our findings thus identify a marker for club cells and reveal a critical role for the BMP noncanonical pathway in club cell regeneration.

中文翻译：

非经典 BMP 信号通路在俱乐部细胞再生中起重要作用

细支气管是发生多种危及生命的疾病的主要部位，包括慢性阻塞性肺疾病和肺腺癌。细支气管上皮由棒状细胞和纤毛上皮细胞组成，棒状细胞作为祖细胞。目前，参与细支气管上皮再生的细胞的身份和潜在机制仍未完全了解。在这里，我们表明 Prrx1，一种同源盒转录因子，可以在体内平衡和再生过程中标记成年小鼠的俱乐部细胞。我们进一步表明，BMP 的非经典信号通路 BMPR1A-Tak1-p38MAPK 在俱乐部细胞再生中起着关键作用。Prrx1+俱乐部细胞中 Bmpr1a、Tak1 或 Mapk14（编码 p38α）的消融对细支气管上皮稳态的影响很小，然而，它导致成年小鼠俱乐部细胞再生和细支气管修复的严重缺陷。我们进一步表明，该途径支持再生俱乐部细胞的增殖和扩张。因此，我们的研究结果确定了俱乐部细胞的标志物，并揭示了 BMP 非经典途径在俱乐部细胞再生中的关键作用。

更新日期：2019-12-06

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