# Cigarette smoke influences alveolar type II cell-derived exosomes

> **NIH NIH R21** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $197,088

## Abstract

Abstract
Alveolar type II (ATII) cells produce and secrete the pulmonary surfactant. They have stem cell potential,
proliferate and restore the epithelium after damage. Emphysema is characterized by alveolar wall destruction. It
is caused by cigarette smoking and second hand smoke. High oxidative stress induced by this exposure leads
to ATII cell injury, mitochondrial and nuclear DNA damage. DNA double-strand breaks (DSBs) pose the most
serious threat to the genomic and mitochondrial DNA. Mitochondrial DNA (mtDNA) is more susceptible
to oxidative damage than nuclear DNA due to the lack of histones that serve as a barrier against damaging
factors as well as limited DNA repair capacity. Failure to repair mtDNA DSBs can trigger a formation of
mutations, deletions and mitophagy. Moreover, damaged mtDNA can be secreted from mitochondria to
the cytoplasm and extracellular space via exosomes. Exosomes are small membrane vesicles that are
released from the cell under normal or pathological conditions. They also serve as signaling vehicles by
delivering proteins, DNA and RNA, to the recipient cells leading to alteration of their gene
expression, proliferation, and differentiation. Furthermore, it has been reported that CD147 regulates
complex I activity in mitochondria and cell apoptosis by interacting with mitochondrial proteins. CD147 is
an extracellular matrix metalloproteinase (MMP) inducer and is known to stimulate MMPs expression. We
detected high mtDNA and CD147 levels in ATII cell-derived exosomes obtained from patients with
emphysema. We will use monoclonal antibody against CD147 to block its harmful function. Our hypothesis is
tinhaetxmotsDoNmAesansdecCrDet1e4d7by ATII cells in emphysema induce injury in the recipient cells. Monoclonal antibody
against CD147 will block circulation of exosomes with harmful content. In Specific Aim #1 we will determine the
function of ATII cell-derived exosomes obtained from emphysema patients. We will study the role of exosomal
mtDNA and CD147 on the recipient ATII cells. In Specific Aim #2, we will determine whether monoclonal antibody
blocking CD147 will decrease the harmful function of exosomes on the recipient cultured ATII cells. Upon
completion of the proposed study, we will have characterized the function of exosomes secreted by ATII cells in
emphysema and their effect on the recipient cells. Monoclonal antibody against exosomal CD147 can provide a
new therapeutic strategy against this disease progression.

## Key facts

- **NIH application ID:** 10164784
- **Project number:** 5R21ES030808-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Karim Bahmed
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,088
- **Award type:** 5
- **Project period:** 2020-05-15 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164784

## Citation

> US National Institutes of Health, RePORTER application 10164784, Cigarette smoke influences alveolar type II cell-derived exosomes (5R21ES030808-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10164784. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*