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Zhang J, Cao K, Pastor JV, et al. Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung. FASEB Bioadv. 2019;1(11):675-687doi: 10.1096/fba.2019-00016.
Zhang, J., Cao, K., Pastor, J. V., Li, L., Moe, O. W., & Hsia, C. C. W. (2019). Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung. FASEB bioAdvances, 1(11), 675-687. https://doi.org/10.1096/fba.2019-00016
Zhang, Jianning, et al. "Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung." FASEB bioAdvances vol. 1,11 (2019): 675-687. doi: https://doi.org/10.1096/fba.2019-00016
Zhang J, Cao K, Pastor JV, Li L, Moe OW, Hsia CCW. Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung. FASEB Bioadv. 2019 Oct 29;1(11):675-687. doi: 10.1096/fba.2019-00016. eCollection 2019 Nov. PMID: 32123814; PMCID: PMC6996373.
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FASEB Bioadv. 2019 Oct 29;1(11):675-687. doi: 10.1096/fba.2019-00016. eCollection 2019 Nov.

Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung.

FASEB bioAdvances

Jianning Zhang, Khoa Cao, Johanne V Pastor, Liping Li, Orson W Moe, Connie C W Hsia

Affiliations

  1. Departments of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA.
  2. Charles and Jane Pak Center of Mineral Metabolism and Clinical Research University of Texas Southwestern Medical Center Dallas TX USA.
  3. Departments of Physiology University of Texas Southwestern Medical Center Dallas TX USA.

PMID: 32123814 PMCID: PMC6996373 DOI: 10.1096/fba.2019-00016

Abstract

Alpha-Klotho (αKlotho), produced by the kidney and selected organs, is essential for tissue maintenance and protection. Homozygous αKlotho-deficiency leads to premature multi-organ degeneration and death; heterozygous insufficiency leads to apoptosis, oxidative stress, and increased injury susceptibility. There is inconsistent data in the literature regarding whether αKlotho is produced locally in the lung or derived from circulation. We probed murine and human lung by immunohistochemistry (IHC) and immunoblot (IB) using two monoclonal (anti-αKlotho Kl1 and Kl2 domains) and three other common commercial antibodies. Monoclonal anti-Kl1 and anti-Kl2 yielded no labeling in lung on IHC or IB; specific labeling was observed in kidney (positive control) and also murine lungs following tracheal delivery of αKlotho cDNA, demonstrating specificity and ability to detect artificial pulmonary expression. Other commercial antibodies labeled numerous lung structures (IHC) and multiple bands (IB) incompatible with known αKlotho mobility; labeling was not abolished by blocking with purified αKlotho or using lungs from hypomorphic αKlotho-deficient mice, indicating nonspecificity. Results highlight the need for rigorous validation of reagents. The lung lacks native αKlotho expression and derives full-length αKlotho from circulation; findings could explain susceptibility to lung injury in extrapulmonary pathology associated with reduced circulating αKlotho levels, for example, renal failure. Conversely, αKlotho may be artificially expressed in the lung, suggesting therapeutic opportunities.

© 2019 The Authors.

Keywords: human; immunoblot; immunohistochemistry; inhalational cDNA delivery; mice; monoclonal antibodies

Conflict of interest statement

The authors have no conflict of interest to declare.

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