title: Delayed re-epithelialization in Ppm1a gene-deficient mice is mediated by enhanced activation of Smad2.
abstract: Protein phosphatase magnesium-dependent 1A (PPM1A), a protein serine/threonine phosphatase, controls several signal pathways through cleavage of phosphate from its substrates. However, the in vivo function of Ppm1a in mammals remains unknown. Here we reported that mice lacking Ppm1a developed normally but were impaired in re-epithelialization process during cutaneous wound healing. Specifically, complete or keratinocyte-specific deletion of Ppm1a led to delayed re-epithelialization with reduced keratinocyte migration upon wounding. We showed that this effect was the result of an increase in Smad2/3 phosphorylation in keratinocytes. Keratinocyte-specific Smad2 deficient mice displayed accelerated re-epithelialization with enhanced keratinocyte migration. Importantly, Smad2 and Ppm1a double mutant mice also exhibited accelerated re-epithelialization, demonstrating that the effect of Ppm1a on promoting re-epithelialization is mediated by Smad2 signaling. Furthermore, the decreased expression of specific integrins and matrix metalloproteinases (MMPs) may contribute to the retarded re-epithelialization in Ppm1a mutant mice. These data indicate that Ppm1a, through suppressing Smad2 signaling, plays a critical role in re-epithelialization during wound healing.
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China; Model Organism Division, E-institutes of Shanghai Universities, Shanghai JiaoTong University, Shanghai 200025, P.R. China.
authors: Xue
authors: X
authors: Yang
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China. Electronic address: tengyan0919@tom.com.
authors: Yan
authors: Y
authors: Teng
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Ning
authors: N
authors: Hou
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China; College of Life Sciences, Hunan Normal University, Changsha 410081, P.R. China.
authors: Xiongwei
authors: X
authors: Fan
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Xuan
authors: X
authors: Cheng
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Jun
authors: J
authors: Li
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Lijuan
authors: L
authors: Wang
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
authors: Youliang
authors: Y
authors: Wang
authors: College of Life Sciences, Hunan Normal University, Changsha 410081, P.R. China.
authors: Xiushan
authors: X
authors: Wu
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China; Model Organism Division, E-institutes of Shanghai Universities, Shanghai JiaoTong University, Shanghai 200025, P.R. China. Electronic address: yangx@nic.bmi.ac.cn.
authors: Xiao
authors: X
authors: Yang
mesh_terms: D000818:Animals; D002465:Cell Movement; D017353:Gene Deletion; D005838:Genotype; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D000071636:Protein Phosphatase 2C; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics*; D014945:Wound Healing
chemical_list: D016023:Integrins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D010749:Phosphoprotein Phosphatases; C000607466:Ppm1a protein, mouse; D000071636:Protein Phosphatase 2C