Changes in PI3K/AKT and NRF2/HO-1 signaling expression and intestinal microbiota in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is the outcome of the prolonged interstitial pneumonia, characterized by excessive accumulation of fibroblasts and collagen deposition, leading to its development. This study aimed to study the changes in PI3K/AKT and NRF2/HO-1 signaling expression and intestinal microbiota in a rat model of a novel bleomycin-induced pulmonary fibrosis. The findings of our study showed the model was successfully established. The results showed that the alveolar septum in the model was significantly widened and infiltrated by severe inflammatory cells. Alveolar atrophy occurred due to the formation of multiple inflammatory foci. During this period, fibrous tissue was distributed in strips and patches, primarily around the pulmonary interstitium and bronchus. Moreover, lung damage and fibrosis progressively worsened over time. The mRNA expression of HO-1 and NRF2 in the model decreased while the mRNA expression of HIF-1α, VEGF, PI3K and AKT increased. Furthermore, it was observed to decrease the protein expression of E-cad, HO-1 and NRF2, and increase the protein expression of α-SMA and p-AKT. Additionally, this model leaded to an imbalance in the intestinal microbiota. This study demonstrate that the novel pulmonary fibrosis model activates the NRF2/HO-1 pathway and the PI3K/AKT pathway in rat lung tissues, and leading to intestinal barrier disorder.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peng Ji reports financial support was provided by National Nature Science Foundation of China. Yanming Wei reports financial support was provided by China's Modern Agricultural Industrial Technology System. Yanming Wei reports financial support was provided by Key R&D Projects of Ningxia Science and Technology Department. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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