Biology subjects

Ermund, A.

Publications and source records attributed to Ermund, A..

3 recordsLinked to original sources

bioRxiv2025

Proteomic analysis of bronchoalveolar lavage fluid after lung transplantation associates stable allograft function with less lung damage at 12 months

IntroductionFreedom from chronic lung allograft dysfunction (CLAD) is a key objective after lung transplantation, yet predicting its onset remains challenging. This study investigated whether early proteomic changes in bronchoalveolar lavage fluid (BALF) can differentiate between patients maintaining stable graft function at 36 months and those developing CLAD within the first year. Additionally, findings were compared to proteomic data from non-transplanted individuals. MethodsBALF samples were collected at one and twelve months post-transplant from 43 lung transplant recipients together with clinical parameters. Proteomic analysis was performed using mass spectrometry with label-free quantification for global protein profiling and heavy-labelled peptides for absolute quantification of mucins and related proteins. Differentially expressed proteins were identified and analyzed through pathway enrichment to explore biological mechanisms associated with CLAD. ResultsNo significant proteomic differences were detected at one month. By twelve months, 63 proteins were differentially expressed between patients who developed early CLAD and those with stable function. Mucin levels declined in stable patients but remained elevated in both groups compared to healthy controls. Cartilage acidic protein 1 was significantly higher in stable patients at twelve months and correlated with better pulmonary function. Pathway analysis linked several altered proteins in CLAD patients to networks associated with lung injury and remodelling. ConclusionProtein profiles in BALF that resemble those of healthy lungs are associated with sustained graft function, while persistent expression of lung injury markers is associated with early CLAD. This suggests an adaptive process is needed for long-term post-transplant success.

molecular biology↗

bioRxiv2024

Anion exchange regulates intestinal mucus expansion while Cftr regulates de novo mucus secretion

The intestinal epithelium is covered by mucus that protects the tissue from the luminal content. Studies have shown that anion secretion via the cystic fibrosis conductance regulator (Cftr) regulates mucus formation in the small intestine. However, mechanisms regulating mucus formation in the colon are less understood. The aim of this study was to explore the role of anion transport in regulation of mucus formation during steady state, and in response to carbamylcholine (CCh) and prostaglandin E2 (PGE2). Cftr{Delta}F508 (CF) mice were used to assess the role of Cftr, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) was used to inhibit anion exchange. In the distal colon, steady state mucus expansion was reduced by apical DIDS, and normal in CF mice. PGE2 stimulated mucus expansion without de novo mucus secretion in wild type (WT) and CF distal colon via DIDS sensitive mechanisms, while CCh induced de novo mucus secretion in WT but not in CF colon. However, when added simultaneously, CCh and PGE2, stimulated de novo mucus secretion in CF colon via DIDS sensitive pathways. A similar response was observed in CF ileum that responded to CCh and PGE2 with DIDS sensitive de novo mucus secretion. In conclusion, this study suggests that apical anion exchange regulates intestinal mucus expansion, while Cftr regulates de novo mucus secretion from ileal and distal colon crypts. Furthermore, these findings demonstrate that in the absence of a functional Cftr channel, activation of anion exchange can help release mucus from intestinal goblet cells.

physiology↗

bioRxiv2017

COPD lungs show an attached stratified mucus layer resembling the protective colonic mucus

The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) mucus accumulates due to goblet cell hyperplasia and mucin overexpression. To address mechanisms behind the mucus accumulation, the elastase-induced mouse model was utilized. The proteomes of bronchoalveolar lavage fluid from elastase-induced mice and COPD patients showed similarities to each other and to colonic mucus. Lung mucus showed a striated, laminated appearance in the elastase-induced mice, COPD and CF, resembling that observed for colonic mucus. Less mucus obstruction was observed in mice lacking the Muc5b mucin. The accumulated mucus plugs of the elastase-induced mice were possible to wash out, but a mucus layer covering the epithelium remained attached to the surface goblet cells also after hypertonic saline washings as widely used in CF therapy. The results suggest that the lung can convert its mucus system into an attached mucus layer that protects the epithelium, similarly to the colon.

physiology↗