Biology subjects

Hakim, S.

Publications and source records attributed to Hakim, S..

4 recordsLinked to original sources

bioRxiv2025

Bigh3 is essential for pulmonary fibrosis

Transforming growth factor beta (TGF-{beta})-induced gene-human, clone 3 (BIGH3) has been implicated as a biomarker of lung fibrosis. However, it is unknown if BIGH3 plays a functional role in fibrosis pathogenesis. To address this question, we used in silico, in vitro and in vivo approaches. We found that BIGH3/Bigh3 is upregulated in human lung fibrosis and mouse models of pulmonary fibrosis. We next generated a novel Bigh3 knockout (Bigh3-/-) mouse and found that while these animals exhibited lung architecture and immune cellularity that is broadly equivalent to wild-type mice, they were protected from lung fibrosis in response to bleomycin administration. In silico modeling suggested that BIGH3 can bind to integrin alpha v (ITGAV). In vitro co-culture systems revealed that activated human lung fibroblasts can elicit BIGH3 expression from human monocyte-derived macrophages. Last, macrophages elicited collagen expression from lung fibroblasts in a manner that is Bigh3-dependent. Collectively, these data suggest that Bigh3 is a product of fibroblast-macrophage interactions that is essential for the pathogenesis of lung fibrosis, possibly via interactions with ITGAV.

immunology↗

bioRxiv2024

Macrophages protect against sensory axon degeneration in diabetic neuropathy

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset and progression of DPN have been linked with dyslipidemia and hyperglycemia3, the contribution of inflammation in the pathogenesis of DPN has not been investigated. Here, we use a High Fat High Fructose Diet (HFHFD) to model DPN and the diabetic metabolic syndrome in mice. Diabetic mice develop persistent heat hypoalgesia after three months, but a reduction in epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, we find that CCR2+ macrophages infiltrate the sciatic nerves of diabetic mice well before axonal degeneration is detectable. We show that these infiltrating macrophages share gene expression similarities with nerve crush-induced macrophages4 and express neurodegeneration-associated microglia marker genes5 although there is no axon loss or demyelination. Inhibiting this macrophage recruitment in diabetic mice by genetically or pharmacologically blocking CCR2 signaling results in a more severe heat hypoalgesia and accelerated skin denervation. These findings reveal a novel neuroprotective recruitment of macrophages into peripheral nerves of diabetic mice that delays the onset of terminal axonal degeneration, thereby reducing sensory loss. Potentiating and sustaining this early neuroprotective immune response in patients represents, therefore, a potential means to reduce or prevent DPN.

neuroscience↗

bioRxiv2023

Nociceptor neuroimmune interactomes reveal cell type- and injury-specific inflammatory pain pathways

Inflammatory pain associated with tissue injury and infections, results from the heightened sensitivity of the peripheral terminals of nociceptor sensory neurons in response to exposure to inflammatory mediators. Targeting immune-derived inflammatory ligands, like prostaglandin E2, has been effective in alleviating inflammatory pain. However, the diversity of immune cells and the vast array of ligands they produce make it challenging to systematically map all neuroimmune pathways that contribute to inflammatory pain. Here, we constructed a comprehensive and updatable database of receptor-ligand pairs and complemented it with single-cell transcriptomics of immune cells and sensory neurons in three distinct inflammatory pain conditions, to generate injury-specific neuroimmune interactomes. We identified cell-type-specific neuroimmune axes that are common, as well as unique, to different injury types. This approach successfully predicts neuroimmune pathways with established roles in inflammatory pain as well as ones not previously described. We found that thrombospondin-1 produced by myeloid cells in all three conditions, is a negative regulator of nociceptor sensitization, revealing a non-canonical role of immune ligands as an endogenous reducer of peripheral sensitization. This computational platform lays the groundwork to identify novel mechanisms of immune-mediated peripheral sensitization and the specific disease contexts in which they act.

neuroscience↗

bioRxiv2020

Metagenomic Analysis of Bacterial Community Associated with Rhizosphere and Phyllosphere of Basmati Rice

Rice is one of the most important crops for feeding about more than half of the worlds population. Yield of rice crop is significantly hampered by various biotic and abiotic factors. Application of cost-effective and environment-friendly bioinoculant is a common practice to combat the yield losses of rice in this era. The rhizosphere and phyllosphere of rice plants provide specific habitats for various micro-organisms. In the present study, the bacterial population dwelling the rhizosphere and phyllosphere of Basmati rice were explored using metagenomic approach from rice growing areas of Punjab, Pakistan. The bacterial communities associated with the rice rhizosphere of different rice growing areas as well as phyllosphere/rhizosphere were compared. Out of 20,069 16S rRNA gene sequences retreived from rhizosphere soil, 6485 were originated from Faisalabad, 5174 from Gujranwala and 8410 from Sheikhupura. Data analyses revelead that Proteobactria was dominant phylum at all three sites. Choloflexi was second abundant phylum at Sheikhupura, while Actinobacteria and Firmicutes at Gujranwala and Faisalabad. In addition to dominant culturable PGPB Bacillus genus at all three sites, Nitrosospira, Gaiella, Marmoricola, Clostridium sensu stricto. Maximum geners were detected from Faisalabad (159), followed by Sheikhupura (146) and Gujranwala (131). Comparison of the common sequences at the genus-level revealed that maximum number of shared genera (101) were observed in Sheikhupura and Gujranwala. 50 genera were specifically related to Faisalabad, while 27 and 21 genera were detected for Sheikhupura and Gujranwala. In the phyllosphere, Proteobacteria (79.6%) was detected as dominant phylum followed by Firmicutes (9.8%), Bacteroidetes (8.6%), Chloroflexi (4.3%) and Actinobacteria (0.9%). Comparison of phyllosphere and rhizosphere showed less bacterial diversity in the phyllosphere but Bradyrhizobium, Sphingomonas, GP6, Pseudomonas, Bacillus are abuundant. Fifteen genera were detected at both compartments. Furthermore, we may select these strains for development of compatible inocula for application in the rhizosphere and phyllosphere of rice.

microbiology↗