Kamakshi Bankoti, PhD
(She/Her/Hers)
Rank
Fellow or Postdoc
Department
Medicine
Pulmonary and Critical Care
Authors
Kamakshi Bankoti*, PhD, Zerihun Negasi, PhD, Mizan Rahman, PhD, Andrea Vendrame, Yohannes Tesfaigzi, PhD.
Principal Investigator
Yohannes Tesfaigzi
Twitter / Website
Categories
Introduction: While the Bcl-2-interacting killer (Bik) is central in inducing cell death in airway epithelial cells (AECs), we have shown that Bik-deficiency leads to emphysema. The present study investigates the molecular mechanisms underlying BIK-deficiency related emphysema.
Methods: Bik+/+ and bik-/- mice were processed for immunostaining with anti-acetylated α-tubulin, anti-CC10, and anti-UCHL1, and the number of ciliated cells, club cells and PNECs, respectively, were quantified. Bik+/+ and bik-/- were intranasally instilled with 50 μg house dust mice allergen (HDM) to investigate the effect of Th2 cytokines in increasing Bik and pulmonary neuroendocrine cell (PNEC) numbers. Mouse tracheal stem cells (MTEC) were infected with an adenoviral Bik expression vector and analyzed for UCHL1. CCSP-rtTA+TetOBik transgenic mice were used to determine the role of Bik in affecting the number of PNECs and reversing emphysema.
Results: Despite lack of proliferation in airways, bik+/+ mice compared with bik-/- mice showed increased PNECs. HDM exposure of bik+/+ mice increased the number of cells expressing Bik and UCHL1-positivity but this increase was reduced in bik-/- mice. Adenoviral overexpression of Bik in MTECs or transgenic expression of Bik in airway of CCSP-rtTA+TetOBik+ mice increased PNEC numbers and reversed spontaneous emphysema of bik-/- mice.
Conclusions: These finding suggest that Bik plays an important role in PNECs maintenance in airway epithelia and this increase was associated with reversal of emphysema. Future studies will explore how PNECs cause the regeneration of the lung parenchyma.
Funding source: RO1HL068111 and R01HL140839