Faruk Hossen

All Publications

• Endothelial Nucleoporin93 (Nup93) Maintains Vascular Function via Sun1-Dependent Regulation of RhoA-eNOS Signaling. bioRxiv : the preprint server for biology Nguyen, T. D., Khan, Y. Z., Hossen, F., Makim, R., Banks, J. M., Michalkiewicz, J., Winek, M. A., de Moraes, L. H., Lee, J. C., Phillips, S. A., Lee, M. Y. 2025

  Abstract

  As the innermost lining of blood vessels, endothelial cells (ECs) regulate blood flow, maintain vascular tone, and limit inflammation for vessel health. EC-derived nitric oxide (NO), synthesized by endothelial nitric oxide synthase (eNOS), is a vasodilator essential for improving blood flow and vascular homeostasis. The RhoA/ROCK pathway regulates eNOS levels, where overactivation decreases eNOS expression and downstream NO production. As such, RhoA/ROCK hyperactivity and increased pMLC have been identified as major contributors to age-associated vasoconstriction and hypertension. Intriguingly, recent studies identify Sun1, a key component of the linker of nucleoskeleton and cytoskeleton (LINC) complex, as a major regulator of RhoA/ROCK activity. Moreover, endothelial aging deteriorates nuclear pore complexes (NPCs) ( i.e. nucleoporin [Nup93]) and impairs nucleocytoplasmic transport, thereby insinuating a role for nuclear envelope components in vessel homeostasis. Here, we show that targeted loss of endothelial Nup93 in adult mice significantly reduces eNOS expression and NO bioavailability for consequent defects in NO-dependent vasodilatory responses. In vitro knockdown of Nup93 in primary human ECs also decreases both eNOS expression and NO production. Mechanistically, we find that loss of Nup93 significantly reduces endothelial Sun1 levels for a concomitant increase in RhoA activity. Indeed, restoring Sun1 protein levels in Nup93-deficient ECs mitigates RhoA activity to rescue both eNOS expression and NO production. Taken together, we demonstrate endothelial Nup93, through Sun1 stabilization, as a novel regulator of eNOS-NO signaling and vessel reactivity, contributing to the growing importance of nuclear membrane components in EC and vascular biology.

  View details for DOI 10.1101/2025.07.18.664980

  View details for PubMedID 40777343

• Oligomeric Amyloid-β and Tau Alter Cell Adhesion Properties and Induce Inflammatory Responses in Cerebral Endothelial Cells Through the RhoA/ROCK Pathway. Molecular neurobiology Hossen, F., Geng, X., Sun, G. Y., Yao, X., Lee, J. C. 2024; 61 (11): 8759-8776

  Abstract

  Dysfunction of cerebral endothelial cells (CECs) has been implicated in the pathology of Alzheimer's disease (AD). Despite evidence showing cytotoxic effects of oligomeric amyloid-β (oAβ) and Tau (oTau) in the central nervous system, their direct effects on CECs have not been fully investigated. In this study, we examined the direct effects of oAβ, oTau, and their combination on cell adhesion properties and inflammatory responses in CECs. We found that both oAβ and oTau increased cell stiffness, as well as the p-selectin/Sialyl-LewisX (sLeX) bonding-mediated membrane tether force and probability of adhesion in CECs. Consistent with these biomechanical alterations, treatments with oAβ or oTau also increased actin polymerization and the expression of p-selectin at the cell surface. These toxic oligomeric peptides also triggered inflammatory responses, including upregulations of p-NF-kB p65, IL-1β, and TNF-α. In addition, they rapidly activated the RhoA/ROCK pathway. These biochemical and biomechanical changes were further enhanced by the treatment with the combination of oAβ and oTau, which were significantly suppressed by Fasudil, a specific inhibitor for the RhoA/ROCK pathway. In conclusion, our data suggest that oAβ, oTau, and their combination triggered subcellular mechanical alterations and inflammatory responses in CECs through the RhoA/ROCK pathway.

  View details for DOI 10.1007/s12035-024-04138-z

  View details for PubMedID 38561558

  View details for PubMedCentralID PMC11445398

• Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway. Free radical biology & medicine Hossen, F., Sun, G. Y., Lee, J. C. 2024; 221: 261-272

  Abstract

  Despite of yet unknown mechanism, microvascular deposition of oligomeric Tau (oTau) has been implicated in alteration of the Blood-Brain Barrier (BBB) function in Alzheimer's disease (AD) brains. In this study, we employed an in vitro BBB model using primary mouse cerebral endothelial cells (CECs) to investigate the mechanism underlying the effects of oTau on BBB function. We found that exposing CECs to oTau induced oxidative stress through NADPH oxidase, increased oxidative damage to proteins, decreased proteasome activity, and expressions of tight junction (TJ) proteins including occludin, zonula occludens-1 (ZO-1) and claudin-5. These effects were suppressed by the pretreatment with Fasudil, a RhoA/ROCK signaling inhibitor. Consistent with the biochemical alterations, we found that exposing the basolateral side of CECs to oTau in the BBB model disrupted the integrity of the BBB, as indicated by an increase in FITC-dextran transport across the model, and a decrease in trans endothelial electrical resistance (TEER). oTau also increased the transmigration of peripheral blood mononuclear cells (PBMCs) in the BBB model. These functional alterations in the BBB induced by oTau were also suppressed by Fasudil. Taken together, our findings suggest that targeting the RhoA/ROCK pathway can be a potential therapeutic strategy to maintain BBB function in AD.

  View details for DOI 10.1016/j.freeradbiomed.2024.05.044

  View details for PubMedID 38815773

  View details for PubMedCentralID PMC11184584

• FAK regulates tension transmission to the nucleus and endothelial transcriptome independent of kinase activity. Cell reports Akhter, M. Z., Yazbeck, P., Tauseef, M., Anwar, M., Hossen, F., Datta, S., Vellingiri, V., Chandra Joshi, J., Toth, P. T., Srivastava, N., Lenzini, S., Zhou, G., Lee, J., Jain, M. K., Shin, J. W., Mehta, D. 2024; 43 (6): 114297

  Abstract

  The mechanical environment generated through the adhesive interaction of endothelial cells (ECs) with the matrix controls nuclear tension, preventing aberrant gene synthesis and the transition from restrictive to leaky endothelium, a hallmark of acute lung injury (ALI). However, the mechanisms controlling tension transmission to the nucleus and EC-restrictive fate remain elusive. Here, we demonstrate that, in a kinase-independent manner, focal adhesion kinase (FAK) safeguards tension transmission to the nucleus to maintain EC-restrictive fate. In FAK-depleted ECs, robust activation of the RhoA-Rho-kinase pathway increased EC tension and phosphorylation of the nuclear envelope protein, emerin, activating DNMT3a. Activated DNMT3a methylates the KLF2 promoter, impairing the synthesis of KLF2 and its target S1PR1 to induce the leaky EC transcriptome. Repleting FAK (wild type or kinase dead) or inhibiting RhoA-emerin-DNMT3a activities in damaged lung ECs restored KLF2 transcription of the restrictive EC transcriptome. Thus, FAK sensing and control of tension transmission to the nucleus govern restrictive endothelium to maintain lung homeostasis.

  View details for DOI 10.1016/j.celrep.2024.114297

  View details for PubMedID 38824643

  View details for PubMedCentralID PMC11262709

• Moringa oleifera is a Prominent Source of Nutrients with Potential Health Benefits. International journal of food science Islam, Z., Islam, S. M., Hossen, F., Mahtab-Ul-Islam, K., Hasan, M. R., Karim, R. 2021; 2021: 6627265

  Abstract

  Nowadays, the socioeconomic status has been changed a lot, so people are now more concerned about their life style and health. They have knowledge about the detrimental effects of synthetic products. That is why they are interested in natural products. Utilization of natural products of plant origin having fewer side effects has gained popularity over the years. There is immense scope for natural products that can intimate health benefits beyond traditional nutrients. Moringa oleifera is one such tree having tremendous nutritional and medicinal benefits. It is rich in macro- and micronutrients and other bioactive compounds which are important for normal functioning of the body and prevention of certain diseases. Leaves, flowers, seeds, and almost all parts of this tree are edible and have immense therapeutic properties including antidiabetic, anticancer, antiulcer, antimicrobial, and antioxidant. Most of the recent studies suggested that Moringa should be used as a functional ingredient in food. The aim of this review is to focus the use of Moringa oleifera as a potential ingredient in food products.

  View details for DOI 10.1155/2021/6627265

  View details for PubMedID 34423026

  View details for PubMedCentralID PMC8373516

• T helper 2-driven immune dysfunction in chronic arsenic-exposed individuals and its link to the features of allergic asthma. Toxicology and applied pharmacology Rahman, A., Islam, M. S., Tony, S. R., Siddique, A. E., Mondal, V., Hosen, Z., Islam, Z., Hossain, M. I., Rahman, M., Anjum, A., Paul, S. K., Hossen, F., Sarker, M. K., Hossain, S., Salam, K. A., Haque, A., Hoque, M. A., Saud, Z. A., Xin, L., Sumi, D., Himeno, S., Hossain, K. 2021; 420: 115532

  Abstract

  Limited information is available regarding the effects of arsenic exposure on immune function. We have recently reported that chronic exposure to As was associated asthma, as determined by spirometry and respiratory symptoms. Because T helper 2 (Th2)-driven immune responses are implicated in the pathogenesis of allergic diseases, including asthma, we studied the associations of serum Th1 and Th2 mediators with the As exposure markers and the features of asthma among individuals exposed to As. A total of 553 blood samples were selected from the same study subjects recruited in our previous asthma study. Serum levels of Th1 and Th2 cytokines were analyzed by immunoassay. Subjects' arsenic exposure levels (drinking water, hair and nail arsenic concentrations) were determined by inductively coupled plasma mass spectroscopy. Arsenic exposure levels of the subjects showed significant positive associations with serum Th2-mediators- interleukin (IL)-4, IL-5, IL-13, and eotaxin without any significant changes in Th1 mediators- interferon-γ and tumor necrosis factor-α. The ratios of Th2 to Th1 mediators were significantly increased with increasing exposure to As. Notably, most of the Th2 mediators were positively associated with serum levels of total immunoglobulin E and eotaxin. The serum levels of Th2 mediators were significantly higher in the subjects with asthma than those without asthma. The results of our study suggest that the exacerbated Th2-driven immune responses are involved in the increased susceptibility to allergic asthma among individuals chronically exposed to As.

  View details for DOI 10.1016/j.taap.2021.115532

  View details for PubMedID 33845054

• Arsenic exposure-related hyperglycemia is linked to insulin resistance with concomitant reduction of skeletal muscle mass. Environment international Mondal, V., Hosen, Z., Hossen, F., Siddique, A. E., Tony, S. R., Islam, Z., Islam, M. S., Hossain, S., Islam, K., Sarker, M. K., Hasibuzzaman, M. M., Liu, L. Z., Jiang, B. H., Hoque, M. M., Saud, Z. A., Xin, L., Himeno, S., Hossain, K. 2020; 143: 105890

  Abstract

  Alargebodyof evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified.We explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia.A total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects' arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-β were used to calculate insulin resistance and β-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators.Water, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-β in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs)of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females' HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia.Arsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.

  View details for DOI 10.1016/j.envint.2020.105890

  View details for PubMedID 32619914

• Association between chronic arsenic exposure and the characteristic features of asthma. Chemosphere Siddique, A. E., Rahman, M., Hossain, M. I., Karim, Y., Hasibuzzaman, M. M., Biswas, S., Islam, M. S., Rahman, A., Hossen, F., Mondal, V., Banna, H. U., Huda, N., Hossain, M., Sultana, P., Nikkon, F., Saud, Z. A., Haque, A., Nohara, K., Xin, L., Himeno, S., Hossain, K. 2020; 246: 125790

  Abstract

  Widespread contamination of arsenic (As) has become a global public health concern. Exposure to As causes respiratory complications. Asthma, a major respiratory complication, is increasing worldwide. However, the effect of chronic As exposure on the risk of asthma remains to be clarified. This study aims to examine the associations between As exposure (water, hair and nail As) and the risk of asthma among 842 individuals exposed to a wide range of As concentrations through drinking water in Bangladesh. Subjects' As exposure levels were measured with ICP-MS. Lung function was examined by a handheld spirometer. Characteristic features of asthma were evaluated by bronchodilator-mediated reversibility in airway obstruction and asthma-like symptoms through a structured questionnaire. Total serum immunoglobulin E (sIgE) levels were measured by immunoassay. As exposure metrics showed inverse associations with lung function measures (FEV1, FEV6, and FEV1/FEV6 ratio) and positive associations with the risks of airway obstruction (AO), reversible airway obstruction (RAO), and asthma-like symptoms. The majority of AO patients (70 of 97) were RAO with one or more characteristic symptoms of asthma. Intriguingly, subjects' As exposure levels showed positive associations with total sIgE levels. Total sIgE in RAO patients was significantly (p < 0.001) higher than that in the control group. Thus the results revealed that chronic As exposure was associated with the risk of the characteristic features of asthma. Additionally the association between As exposure and subjects' total sIgE levels and an elevated level of total sIgE in RAO group suggested that As exposure-related asthma might be allergic in nature.

  View details for DOI 10.1016/j.chemosphere.2019.125790

  View details for PubMedID 31918100

• Dose-dependent relationships between chronic arsenic exposure and cognitive impairment and serum brain-derived neurotrophic factor. Environment international Karim, Y., Siddique, A. E., Hossen, F., Rahman, M., Mondal, V., Banna, H. U., Hasibuzzaman, M. M., Hosen, Z., Islam, M. S., Sarker, M. K., Nikkon, F., Saud, Z. A., Xin, L., Himeno, S., Hossain, K. 2019; 131: 105029

  Abstract

  Arsenic poisoning is a public health problem worldwide. A few studies have reported the effects of arsenic exposure on adult cognitive function, but with limitations in the subject selection and exposure markers. Moreover, information regarding the association between arsenic exposure and biomarker of cognitive impairment is scarce.We examined the associations between arsenic exposure and adult cognitive impairment using the Mini-Mental State Examination (MMSE) and the serum levels of brain-derived neurotrophic factor (BDNF), a potential biomarker of cognitive health status.We designed a cross-sectional study that recruited 693 adult (18-60 years old) subjects from the areas of low- and high‑arsenic exposure in rural Bangladesh. The subjects' arsenic exposure levels (drinking water, hair, and nail arsenic concentrations) were measured by inductively coupled plasma-mass spectroscopy. The Bangla version of the MMSE was used as a cognitive assessment tool. Serum BDNF (sBDNF) levels were assessed by immunoassay.In this study, we found that average MMSE score and sBDNF level of the subjects in arsenic-endemic areas were significantly (p < 0.001 for both) lower than those of the subjects in non-endemic area. Our analyses revealed that both MMSE scores and sBDNF levels were decreased with the increasing concentrations of arsenic in drinking water, hair, and nails in a dose-dependent fashion. In regression analyses, significant associations of arsenic exposure metrics with MMSE scores and sBDNF levels were observed even after adjustment for several variables. Intriguingly, MMSE scores showed a significantly positive correlation with sBDNF levels.Our findings demonstrate that chronic exposure to arsenic dose-dependently decreases cognitive function in adults, with a concomitant reduction of sBDNF levels. A decreased BDNF level may be part of the biochemical basis of chronic arsenic exposure-related cognitive impairment.

  View details for DOI 10.1016/j.envint.2019.105029

  View details for PubMedID 31352261