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The noncanonical BMP signaling pathway plays an important role in club cell regeneration
dc.contributor.authorShafiquzzaman, Md
dc.contributor.authorBiswas, Soma
dc.contributor.authorLi, Ping
dc.contributor.authorMishina, Yuji
dc.contributor.authorLi, Baojie
dc.contributor.authorLiu, Huijuan
dc.date.accessioned2020-03-17T18:27:20Z
dc.date.availableWITHHELD_13_MONTHS
dc.date.available2020-03-17T18:27:20Z
dc.date.issued2020-03
dc.identifier.citationShafiquzzaman, Md; Biswas, Soma; Li, Ping; Mishina, Yuji; Li, Baojie; Liu, Huijuan (2020). "The noncanonical BMP signaling pathway plays an important role in club cell regeneration." STEM CELLS 38(3): 437-450.
dc.identifier.issn1066-5099
dc.identifier.issn1549-4918
dc.identifier.urihttps://hdl.handle.net/2027.42/154263
dc.description.abstractThe 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.Schematic representation of our results showing the critical roles of the noncanonical signaling pathway of BMPs, (BMPR1A‐Tak1‐p38MAPK) in club cell regeneration. Naphthalene (NA) is metabolized by CYP‐2F2, which is expressed exclusively in club cells, generating cytotoxic epoxide that kills the club cells within 1.5 days after NA exposure. Under normal conditions, hyperplastic growth occurs at day 3 and the bronchiolar epithelium is restored at day 7. We show that ablation of Bmpr1a, Tak1, or Mapk14 (encoding p38α) in club cells resulted in severe defects in regeneration and bronchiole repair in adult mice.
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otherclub cell regeneration
dc.subject.othernoncanonical BMP pathway
dc.subject.otherclub cells
dc.subject.otherbronchiolar epithelium
dc.subject.otherPrrx1
dc.subject.otherTak1‐p38MAPK
dc.titleThe noncanonical BMP signaling pathway plays an important role in club cell regeneration
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154263/1/stem3125_am.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154263/2/stem3125.pdf
dc.identifier.doi10.1002/stem.3125
dc.identifier.sourceSTEM CELLS
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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