Biomaterial Database

Intrinsic BMP inhibitor Gremlin regulates alveolar epithelial type II cell proliferation and differentiation. 2023

Toyoshi Yanagihara, and Quan Zhou, and Kazuya Tsubouchi, and Spencer Revill, and Anmar Ayoub, and Mahsa Gholiof, and Sy Giin Chong, and Anna Dvorkin-Gheva, and Kjetil Ask, and Wei Shi, and Martin Rj Kolb

Firestone Institute for Respiratory Health, Research Institute at St Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Type 1 alveolar epithelial cells (AT1s) and type 2 alveolar epithelial cells (AT2s) regulate the structural integrity and function of alveoli. AT1s mediate gas exchange, whereas AT2s serve multiple functions, including surfactant secretion and alveolar repair through proliferation and differentiation into AT1s as progenitors. However, mechanisms regulating AT2 proliferation and differentiation remain unclear. Here we demonstrate that Gremlin, an intrinsic inhibitor of bone morphogenetic protein (BMP), induces AT2 proliferation and differentiation. Transient overexpression of Gremlin in rat lungs by adenovirus vector delivery suppressed BMP signaling, induced proliferation of AT2s and the production of Bmp2, which in turn led to the recovery of BMP signaling and induced AT2 differentiation into AT1s. Bleomycin-induced lung injury upregulated Gremlin and showed a similar time course of biomarker expression comparable to the adenovirus model. TGF-β and IL-1β induced Gremlin expression in fibroblasts. Taken together, our findings implicate that Gremlin expression during lung injury leads to precisely timed inhibition of BMP signaling and activates AT2s, leading to alveolar repair.

UI	MeSH Term	Description	Entries
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D049109	Cell Proliferation	All of the processes involved in increasing CELL NUMBER including CELL DIVISION.	Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055370	Lung Injury	Damage to any compartment of the lung caused by physical, chemical, or biological agents which characteristically elicit inflammatory reaction. These inflammatory reactions can either be acute and dominated by NEUTROPHILS, or chronic and dominated by LYMPHOCYTES and MACROPHAGES.	E-Cigarette Use-Associated Lung Injury,E-Cigarette or Vaping Product Use-Associated Lung Injury,EVALI,Vaping Product Use-Associated Lung Injury,Chronic Lung Injury,Lung Injuries,Pulmonary Injury,Chronic Lung Injuries,E Cigarette Use Associated Lung Injury,E Cigarette or Vaping Product Use Associated Lung Injury,EVALIs,Injuries, Lung,Injuries, Pulmonary,Injury, Lung,Injury, Pulmonary,Lung Injuries, Chronic,Lung Injury, Chronic,Pulmonary Injuries,Vaping Product Use Associated Lung Injury
D056809	Alveolar Epithelial Cells	Epithelial cells that line the PULMONARY ALVEOLI.	Pneumocytes,Alveolar Cells,Pneumocyte,Type 1 Pneumocytes,Type 2 Pneumocytes,Type-I Pneumocytes,Type-II Pneumocytes,Alveolar Cell,Alveolar Epithelial Cell,Cell, Alveolar,Cell, Alveolar Epithelial,Cells, Alveolar,Cells, Alveolar Epithelial,Epithelial Cell, Alveolar,Epithelial Cells, Alveolar,Pneumocyte, Type 1,Pneumocyte, Type 2,Pneumocyte, Type-I,Pneumocyte, Type-II,Pneumocytes, Type 1,Pneumocytes, Type 2,Pneumocytes, Type-I,Pneumocytes, Type-II,Type 1 Pneumocyte,Type 2 Pneumocyte,Type I Pneumocytes,Type II Pneumocytes,Type-I Pneumocyte,Type-II Pneumocyte
D019485	Bone Morphogenetic Proteins	Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.	Bone Morphogenetic Protein,Morphogenetic Protein, Bone,Morphogenetic Proteins, Bone