{"id":2598,"date":"2026-06-30T13:14:48","date_gmt":"2026-06-30T08:14:48","guid":{"rendered":"https:\/\/journal.nncf.kz\/?p=2598"},"modified":"2026-07-03T23:19:57","modified_gmt":"2026-07-03T18:19:57","slug":"%d0%b1%d1%80%d0%be%d0%bd%d1%85%d0%be%d0%bb%d0%b5%d0%b3%d0%be%d1%87%d0%bd%d0%b0%d1%8f-%d0%b4%d0%b8%d1%81%d0%bf%d0%bb%d0%b0%d0%b7%d0%b8%d1%8f-%d0%be%d1%82-%d0%bd%d0%b0%d1%80%d1%83%d1%88%d0%b5%d0%bd","status":"publish","type":"post","link":"https:\/\/journal.nncf.kz\/en\/%d0%b1%d1%80%d0%be%d0%bd%d1%85%d0%be%d0%bb%d0%b5%d0%b3%d0%be%d1%87%d0%bd%d0%b0%d1%8f-%d0%b4%d0%b8%d1%81%d0%bf%d0%bb%d0%b0%d0%b7%d0%b8%d1%8f-%d0%be%d1%82-%d0%bd%d0%b0%d1%80%d1%83%d1%88%d0%b5%d0%bd\/","title":{"rendered":"BRONCHOPULMONARY DYSPLASIA: FROM IMPAIRED ALVEOLOGENESIS TO MOLECULAR AND CELLULAR DYSREGULATION IN PRETERM NEWBORNS"},"content":{"rendered":"

Received by the Editorial Office: May 15, 2026 <\/em><\/p>\n

Accepted for publication: June 14, 2026 <\/em><\/p>\n

Published online: June 30, 2026<\/em><\/p>\n

\u0423\u0414\u041a: 616.24-008.4-053.32<\/p>\n

DOI: 10.26212\/2227-1937.2026.26.79.007<\/a><\/p>\n

 <\/p>\n

BRONCHOPULMONARY DYSPLASIA: FROM IMPAIRED ALVEOLOGENESIS TO MOLECULAR AND CELLULAR DYSREGULATION IN PRETERM NEWBORNS<\/strong><\/p>\n

\u00a0<\/strong><\/p>\n

Abilbayeva A.A.1<\/sup>,<\/strong> Shaktay N.K.1<\/sup>,\u00a0Tarabayeva A.S.1<\/sup>, <\/strong><\/p>\n

Kuat A.<\/strong>1<\/sup><\/strong>, <\/strong>Nurym K.<\/strong>1<\/sup><\/strong>, <\/strong>Sagidulla A.<\/strong>1<\/sup><\/strong><\/p>\n

1<\/sup><\/em>Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan<\/em><\/p>\n

\u00a0<\/strong><\/p>\n

Introduction<\/strong>. <\/strong>Bronchopulmonary dysplasia (BPD) remains the most common chronic lung disease in preterm neonates, particularly those with very low birth weight. The “new BPD” paradigm has shifted from the classical injury-driven fibrosis toward a process characterized by arrested alveolar development and vascular dysgenesis. This condition results in a reduced surface area for gas exchange due to the formation of fewer, simplified alveoli and impaired angiogenesis.<\/p>\n

Objective<\/strong>. <\/strong>The purpose of this review is to provide an integrative analysis of the cellular and molecular dysregulation driving BPD pathogenesis, focusing on the disruption of intercellular signaling networks that govern alveolar morphogenesis and vascular development in the immature preterm lung.<\/p>\n

Materials and Methods<\/strong>. <\/strong>An integrative narrative literature review was performed. The electronic databases PubMed and Google Scholar were systematically searched for articles published between January 2010 and March 2025. Search queries included the terms “bronchopulmonary dysplasia”, “alveologenesis”, “angiogenesis”, “signaling pathways”, “lung development” and “preterm infants”. Only articles published in English were considered. Inclusion criteria comprised peer-reviewed original research articles and comprehensive review articles that directly addressed molecular, cellular, or signaling mechanisms of BPD or normal alveologenesis. Exclusion criteria encompassed conference abstracts, non-peer-reviewed sources, editorials lacking primary data, and studies without sufficient methodological detail. Duplicate records were manually removed prior to full-text screening. Of the 374 unique records identified, 301 were excluded following title and abstract screening. The remaining 73 articles met all inclusion criteria after full-text review and were incorporated into the final synthesis. This review is integrative and narrative. It does not meet the formal criteria for a systematic review, as a non-systematic selection flowchart was generated and no inter-rater agreement or quality assessment tool was used.<\/p>\n

Results.<\/strong> A synthesis of 73 publications, including experimental studies, transcriptomic and proteomic analyses, clinical investigations, and review articles, identified three pathogenetic mechanisms with the highest degree of evidentiary support. PDGFR\u03b1-dependent depletion and proliferative failure of alveolar myofibroblasts emerged as the central driver of alveolar simplification, corroborated by convergent preclinical and clinical genetic data. VEGF-A deficiency was established as the molecular correlate of capillary dysplasia, documented both in fatal human BPD and across multiple animal models. TGF-\u03b2 hyperproduction was identified as the principal pro-fibrotic and anti-septogenic signal that concurrently suppresses VEGF-A expression, thereby amplifying vascular and structural deterioration. Normal alveologenesis depends on coordinated interactions among four functionally interdependent cellular systems, namely the alveolar epithelium represented by ATII and ATI cells, the pulmonary mesenchyme including secondary-crest myofibroblasts and lipofibroblasts, the vascular endothelium, and the extracellular matrix. Disruption of this intercellular network at multiple levels constitutes the pathobiological basis of BPD. Mesenchymal stromal cell-based therapy demonstrates consistent efficacy in preclinical models. However, its clinical translation remains limited by the absence of Phase III randomized controlled trial data in preterm neonates.<\/p>\n

Discussion.<\/strong> The synthesized evidence indicates that BPD should be interpreted not as isolated epithelial, vascular, or mesenchymal injury, but as a disorder of coordinated lung development. The convergence of PDGFR\u03b1 attenuation, VEGF-A deficiency, and TGF-\u03b2 overactivation supports a hierarchical pathogenetic model in which impaired myofibroblast function initiates defective septation and secondarily disrupts vascular growth. At the same time, much of the mechanistic evidence is derived from animal and preclinical models; therefore, translation into neonatal practice requires cautious interpretation and validation in adequately powered clinical studies.<\/p>\n

Conclusion<\/strong>. BPD represents a significant failure of lung development, primarily resulting from impaired intercellular communication. The characteristic structural abnormalities, including alveolar simplification and vascular dysmorphism, arise from disrupted regenerative capacity within the lung. Attenuation of PDGFR\u03b1-dependent myofibroblast function is identified as the central upstream event, leading to secondary suppression of VEGF-A and subsequent capillary dysplasia. TGF-\u03b2 further exacerbates structural deterioration. Effective therapeutic strategies should focus on restoring the myofibroblast-VEGF-extracellular matrix axis as an integrated system rather than targeting individual components. This approach may support lasting repair of alveolar and vascular structures in preterm infants.<\/p>\n

Keywords: <\/strong>Bronchopulmonary dysplasia, alveologenesis, angiogenesis, preterm neonates, signaling pathways, lung development.<\/p>\n

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