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The Journal of biological chemistry
Dec 09, 2011;286 (49): 42267-42273.

Delayed re-epithelialization in Ppm1a gene-deficient mice is mediated by enhanced activation of Smad2.

Xue Yang, Yan Teng, Ning Hou, Xiongwei Fan, Xuan Cheng, Jun Li, Lijuan Wang, Youliang Wang, Xiushan Wu, Xiao Yang
Author Information
  1. Xue Yang: 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.
  2. Yan Teng: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China. Electronic address: tengyan0919@tom.com.
  3. Ning Hou: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
  4. Xiongwei Fan: 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.
  5. Xuan Cheng: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
  6. Jun Li: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
  7. Lijuan Wang: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
  8. Youliang Wang: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, P.R. China.
  9. Xiushan Wu: College of Life Sciences, Hunan Normal University, Changsha 410081, P.R. China.
  10. Xiao Yang: 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.
PMID: 21990361 DOI: 10.1074/jbc.M111.292284

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.

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MeSH Term

Animals
Cell Movement
Gene Deletion
Genotype
Integrins
Keratinocytes
Mice
Mice, Knockout
Mice, Transgenic
Models, Genetic
Mutation
Phosphoprotein Phosphatases
Protein Phosphatase 2C
Signal Transduction
Smad2 Protein
Wound Healing

Chemicals

Integrins
Smad2 Protein
Smad2 protein, mouse
Phosphoprotein Phosphatases
Ppm1a protein, mouse
Protein Phosphatase 2C
Journal Article Research Support, Non-U.S. Gov't

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