Influence of obesity on remodeling of lung tissue and organization of extracellular matrix after blunt thorax trauma

Respiratory Research

Timo Burster¹  Fabian Gärtner²  Uwe Knippschild²  Pengfei Xu²  Stephan Paschke²  Adrian Gihring²  Congxing Liu²  Martin Wabitsch³ 

[1] Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave., 53, 010000, Nur-Sultan, Republic of Kazakhstan;Department of General and Visceral Surgery, Surgery Center; Ulm University Medical Center, Albert-Einstein-Allee 23, 89081, Ulm, Germany;Division of Pediatric Endocrinology and Diabetes, Ulm University Hospital for Pediatrics and Adolescent Medicine, Eythstraße 24, 89075, Ulm, Germany;

关键词: Obesity;    High fat diet;    Thorax trauma;    Extracellular matrix (ECM);    Collagen;    MMP activity;    TIMP production;   

DOI  :  10.1186/s12931-020-01502-0

来源: Springer

【 摘 要 】

BackgroundPreviously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet.MethodsThis study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h).ResultsMorphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%.ConclusionsIn conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.

【 授权许可】

CC BY