Biology subjects

Mensah, E.

Publications and source records attributed to Mensah, E..

4 recordsLinked to original sources

bioRxiv2025

A Simultaneous Inhibition of ID1 and ID3 Protects Against Pulmonary Fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which novel therapeutic approaches are desperately needed. Inhibitor of DNA binding (ID) proteins are regulated by Transforming Growth Factor-{beta}. However, the regulation and the effects of ID proteins in IPF remain poorly understood. We aimed to assess the expression of ID proteins in IPF and determine the effects of ID proteins on human lung fibroblasts (HLF) in vitro and pulmonary fibrosis in vivo. MethodsThe expression of ID proteins in lungs and lung fibroblasts from mice and human patients with pulmonary fibrosis was evaluated. The effects of ID1/ID3 inhibition and overexpression on HLF were assessed. Genetic and pharmacological approaches were used in vivo to determine the role of ID1/ID3 in pulmonary fibrosis. ResultsID1/ID3 levels were elevated in HLFs isolated from pulmonary fibrosis-diseased patients and mice. ID1/ID3 knockdown decreased IPF-diseased HLF proliferation and differentiation into myofibroblasts. Bleomycin-exposed ID1/ID3 KO mice displayed improved lung function and presented with decreased lung fibrosis when compared to WT mice. A pharmacological inhibitor of ID1/ID3 decreased IPF-diseased HLF proliferation and differentiation in vitro and attenuated pulmonary fibrosis in vivo. A lung specific inhibition of ID1/ID3, using adeno-associated viruses expressing short hairpins targeting ID1 and ID3, reversed pulmonary fibrosis in mice. Mechanistically, ID1/ID3 inhibition decreased fibroblast proliferation through cell cycle genes and inhibited fibroblast differentiation through the MEK/ERK pathway. ConclusionsOur data indicate that a simultaneous inhibition of ID1 and ID3 attenuates pulmonary fibrosis. ID1/ID3 inhibition holds potential as a novel therapeutic treatment for IPF.

pathology↗

bioRxiv2025

Paracrine Action of Bone Morphogenetic Protein 3 in Pulmonary Arterial Hypertension

BackgroundDespite recent advancements in the management of pulmonary arterial hypertension (PAH), the disease remains devastating, with limited survival. Although the Bone Morphogenetic Protein (BMP) signaling pathway is known to play an important role in PAH, our current understanding of this pathway remains limited. MethodsWe assessed BMP3 levels in the lungs of mice, rats, and pigs with pulmonary hypertension, and in pulmonary vascular cells from human patients with PAH. We performed in vitro studies on human pulmonary artery smooth muscle cells (hPASMCs) and human pulmonary artery endothelial cells (hPAECs) derived from healthy donors and from patients with PAH. We generated mice with global or SMC-specific deletion of BMP3. Recombinant BMP3 protein and adeno-associated viruses (AAV) were used to overexpress BMP3 in two different models of PAH in rodents. Magnetic resonance imaging, cardiac hemodynamics, morphometric, and histological measurements were performed to evaluate the effects of BMP3 on cardiac function and pulmonary vascular remodeling. ResultsBMP3 is predominantly expressed in PASMCs and is downregulated in PAH. In vitro, conditioned medium from siRNA-BMP3-transfected hPASMCs increased hPAECs migration and proliferation, while PASMC-derived BMP3 inhibited PAH-diseased PAEC dysfunction. In both global and SMC-specific BMP3-deficient mice, exposure to a model of PAH exacerbated cardiac and pulmonary vascular remodeling in middle-aged mice. An intraperitoneally injected recombinant BMP3 prevented and reversed PAH in mice. A lung-targeted overexpression of BMP3, via AAV1-BMP3, reversed pulmonary vascular remodeling and inhibited cardiac dysfunction in mice and rats. Mechanistically, BMP3 activated the BMP/Smad1,5,8 pathway, inhibited the TGF-{beta}/Smad2,3 pathway, and decreased the expression of cell cycle genes in hPAECs and in the lungs of BMP3-treated animals with PAH. ConclusionsOur findings provide evidence that BMP3 overexpression attenuates pulmonary vascular remodeling and inhibits cardiac dysfunction by restoring the balance between the TGF-{beta} and BMP pathways through a cell-cell communication mechanism, offering a novel therapeutic pathway for PAH. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LIBMP3 is downregulated in the lungs of mice, rats, and pigs with pulmonary hypertension and in pulmonary artery smooth muscle cells of patients with PAH. C_LIO_LIBMP3 acts as a paracrine factor between pulmonary vascular cells. C_LIO_LIOverexpression of BMP3 decreases pulmonary vascular remodeling and reverses cardiac dysfunction in PAH-diseased rodents. C_LIO_LIBMP3 acts by restoring the balance between the TGF-{beta}/Smad2,3 pathway and the BMP/Smad1,5,8 pathway C_LI What Are the Clinical Implications?O_LIBMP3 represents a promising disease-modifying agent with potential for clinical translation in the treatment of PAH. C_LIO_LIOverexpressing BMP3 with Adeno-Associated Viruses has therapeutic potential to treat PAH. C_LI

pathology↗

bioRxiv2019

Transactional sex among men who have sex with men participating in the CohMSM prospective cohort study in West Africa

Men who have sex with men (MSM) are at much greater risk of HIV infection in Africa. Little is known about their involvement in transactional sex (TS). We aimed to characterize MSM reporting TS (MSM-TS) and to identify factors associated with their sexual practices using data from the prospective cohort study CohMSM conducted in Burkina Faso, Cote dIvoire, Mali and Togo. Our study focused on HIV-negative MSM, recruited between 06/2015 and 01/2018 by a team of trained peer educators. Scheduled study visits at 6, 12 and 18 months included medical examinations, HIV screening, risk-reduction counselling and face-to-face interviews to collect information on their sociodemographic characteristics, sexual behaviours, and HIV risk-reduction strategies. Three stigmatization sub-scores were constructed. The generalized estimating equation method was used for data analysis. Of the 630 HIV-negative participants recruited at baseline, 463, 410 and 244 had a follow-up visit at 6- and 12- and 18-months, respectively. Over a total of 1747 visits, 478 TS encounters were reported by 289 MSM-TS (45.9%). Of the latter, 91 participants reported systematic TS (31.5%), 55 (19.0 %) stopped reporting TS after baseline, and 53 (18.3%) reported TS after baseline. Ninety participants (31.1 %) reported occasional TS. After adjusting for country of study and follow-up visits, the following factors, reported for the previous 6 months, were associated with a greater likelihood of TS: younger age, an educational level <high-school diploma, satisfaction with current sex life, group sex with men, multiple male sexual partners, condomless anal sex, receptive or versatile anal sex with male sexual partners, giving benefits in exchange for sex with a man, alcohol consumption and drug use during sex, and experiencing stigmatization. The majority of MSM in this study who received benefits in exchange for sex had high-risk HIV infection exposure practices and were characterized by socioeconomic difficulties.

epidemiology↗

bioRxiv2019

Male clients of male sex workers in West Africa: A neglected high risk population

Research on male clients of male sex workers (MCMSW) has been neglected for a long time globally. We aimed to characterize MCMSW and to identify factors associated with their sexual practices using data from the prospective cohort study CohMSM conducted in Burkina Faso, Cote dIvoire, Mali and Togo. Our study focused on HIV-negative men who have sex with other men (MSM) recruited between 06/2015 and 01/2018 by a team of trained peer educators. Scheduled study visits at 6, 12 and 18 months included medical examinations, HIV screening, risk-reduction counselling and face-to-face interviews to collect information on their sociodemographic characteristics, sexual behaviours, and HIV risk-reduction strategies (HIV-RRS). Three stigmatization sub-scores were constructed (experienced, perceived and internalized). Mixed-effects logistic regression was used for data analysis. Of the 280 participants recruited at baseline, 238, 211 and 118, respectively, had a follow-up visit at 6, 12 and 18 months. Over a total of 847 visits, 47 transactional sex (TS) encounters were reported by 38 MCMSW (13.6%). Of the latter, only one participant reported systematic TS (2.6%), 18 (47.4 %) stopped reporting TS after baseline, and 6 (15.8%) reported TS after baseline. Thirteen participants (34.2 %) reported occasional TS. After adjusting for country of study and age, the following self-reported factors were associated with a greater likelihood of being MCMSW: protected anal sex, exclusively insertive anal sex with male sexual partners, avoidance of sex after consuming psychoactive products and experiencing stigmatization (all during the previous 6 months). The majority of MCMSW in this study employed HIV-RRS with male sexual partners, including engaging in protected anal sex, avoidance of sex when consuming psychoactive products, and practising exclusively insertive anal sex.

epidemiology↗