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Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia

  • Authors:
    • Kang Li
    • Luobu Gesang
    • Zeng Dan
    • Lamu Gusang
  • View Affiliations / Copyright

    Affiliations: High Altitude Medical Research Institute, People's Hospital of Tibet Autonomous Region, Lhasa 850000, P.R. China, Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, P.R. China, Department of Cardiology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 287-296
    |
    Published online on: December 14, 2016
       https://doi.org/10.3892/ijmm.2016.2830
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Abstract

High altitude-associated polycythemia (HAPC) is a very common disease. However, it the disease is still unmanageable and the related molecular mechanisms remain largely unclear. In the present study, we aimed to explore the molecular mechanisms responsible for the development of HAPC using transcriptome analysis. Transcriptome analysis was conducted in 3 pairs of gastric mucosa tissues from patients with HAPC and healthy residents at a similar altitude. Endoscopy and histopathological analyses were used to examine the injury to gastric tissues. Molecular remodeling was performed for the interaction between different KLK members and cholesterol. HAPC was found to lead to morphological changes and pathological damage to the gastric mucosa of patients. A total of 10,304 differentially expressed genes (DEGs) were identified. Among these genes, 4,941 DEGs were upregulated, while 5,363 DEGs were downregulated in the patients with HAPC (fold change ≥2, P<0.01 and FDR <0.01). In particular, the kallikrein gene cluster (KLK1/3/7/8/12) was upregulated >17-fold. All the members had high-score binding cholesterol, particularly for the polymers of KLK7. The kallikrein gene cluster (KLK1/3/7/8/12) is on chromosome 19q13.3-13.4. The elevated levels of KLK1, KLK3, KLK7, KLK8 and KLK12 may be closely associated with the hypertension, inflammation, obesity and other gastric injuries associated with polycythemia. The interaction of KLKs and cholesterol maybe play an important role in the development of hypertension. The findings of the present study revealed that HAPC induces gastric injury by upregulating the kallikrein gene cluster (KLK1/3/7/8/12), which can bind cholesterol and result in kallikrein hypertension. These findings provide some basic information for understanding the molecular mechanisms responsible for HAPC and HAPC-related diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Li K, Gesang L, Dan Z and Gusang L: Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia. Int J Mol Med 39: 287-296, 2017.
APA
Li, K., Gesang, L., Dan, Z., & Gusang, L. (2017). Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia. International Journal of Molecular Medicine, 39, 287-296. https://doi.org/10.3892/ijmm.2016.2830
MLA
Li, K., Gesang, L., Dan, Z., Gusang, L."Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia". International Journal of Molecular Medicine 39.2 (2017): 287-296.
Chicago
Li, K., Gesang, L., Dan, Z., Gusang, L."Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia". International Journal of Molecular Medicine 39, no. 2 (2017): 287-296. https://doi.org/10.3892/ijmm.2016.2830
Copy and paste a formatted citation
x
Spandidos Publications style
Li K, Gesang L, Dan Z and Gusang L: Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia. Int J Mol Med 39: 287-296, 2017.
APA
Li, K., Gesang, L., Dan, Z., & Gusang, L. (2017). Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia. International Journal of Molecular Medicine, 39, 287-296. https://doi.org/10.3892/ijmm.2016.2830
MLA
Li, K., Gesang, L., Dan, Z., Gusang, L."Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia". International Journal of Molecular Medicine 39.2 (2017): 287-296.
Chicago
Li, K., Gesang, L., Dan, Z., Gusang, L."Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia". International Journal of Molecular Medicine 39, no. 2 (2017): 287-296. https://doi.org/10.3892/ijmm.2016.2830
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