Targeting basal cell-mediated epithelial repair: preclinical evidence on their role in treating chronic obstructive pulmonary disease (COPD)

GADJDJOE, PHOEJA (2021) Targeting basal cell-mediated epithelial repair: preclinical evidence on their role in treating chronic obstructive pulmonary disease (COPD). Bachelor's Thesis, Pharmacy.

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Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease that is characterized by chronic inflammation and airflow obstruction due to airway remodeling, leading to a decline in lung function. COPD is the fourth most common cause of death and affects the daily lives of millions of patients globally. There are currently no curative treatments, meaning novel treatments are greatly desired. When lungs are injured, various progenitor cells, including basal cells, proliferate to restore the epithelium layer. However, upon persistent injury, basal cells lose their ability to do so. This literature review therefore aimed to evaluate the therapeutic potential of stimulating basal cell functionality in COPD via Hedgehog and Notch signaling pathways to induce epithelial repair. Taken together, evaluated studies showed inhibition or downregulation of Hhip, Ptch1 and Notch 2 receptors (via Hhip, Ptch1 or Notch 2 antagonists) and upregulation or activation of the SHH ligand (via a SHH agonist) in HH and Notch signaling pathways may be therapeutically beneficial as both lead to increased basal stem/progenitor cells and a balanced differentiation into secretory and multiciliated cells, thereby inducing epithelial repair at the earliest stages of COPD progression. These therapeutic strategies should be evaluated using a combination of cigarette smoke - and elastase induced mice models, lung organoids (of basal progenitor cells) and clinical studies.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Ruigrok, M.J.R.
Degree programme:	Pharmacy
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	08 Apr 2021 08:32
Last Modified:	08 Apr 2021 08:32
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/24218

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