A New Rat Model of Sacral Cord Injury Producing a Neurogenic Bladder and Its Functional and Mechanistic Studies DOI Creative Commons
Kaiping Bai, Yanping Hou, Zhiyuan Zhang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1141 - 1141

Published: Sept. 9, 2024

Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI better understand disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation groups. The group underwent sacral injury, while did not. Urodynamic histological assessments conducted at various intervals (1, 2, 3, 4, 6 weeks) post-injury elucidate process. examinations revealed significant compared group, stabilizing around 3–4 weeks post-injury. Histological examination, including hematoxylin–eosin Masson’s trichrome staining, correlated these functional microstructural alterations. RNA-seq was performed tissues from identify differentially expressed genes pathways. Selected further analyzed using polymerase chain reaction (PCR). findings indicated pronounced inflammatory response first 2 post-SSCI, progressing fibrosis weeks. In conclusion, this presents reliable, reproducible, straightforward model, providing insights morphological alterations post-SSCI laying groundwork for future therapeutic research.

Language: Английский

Female fibroblast activation is estrogen-mediated in sex-specific 3D-bioprinted pulmonary artery adventitia models DOI Open Access

Mikala C. Mueller,

Rachel Blomberg, Alicia E. Tanneberger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Pulmonary arterial hypertension (PAH) impacts male and female patients in different ways. Female exhibit a greater susceptibility to disease (4:1 female-to-male ratio) but live longer after diagnosis than patients. This complex sexual dimorphism is known as the estrogen paradox. Prior studies suggest that signaling may be pathologic pulmonary vasculature protective heart, yet mechanisms underlying these sex-differences PAH remain unclear. form of vascular results scarring small blood vessels, leading impaired flow increased pressure. Over time, this increase pressure causes damage heart. Many previous relied on cells or undisclosed origin for vitro modeling. Here we present dynamic, 3D-bioprinted model incorporates circulating sex hormones from specifically study how respond changes microenvironmental stiffness hormone signaling. Poly(ethylene glycol)-alpha methacrylate (PEGαMA)-based hydrogels containing human artery adventitia fibroblasts (hPAAFs) idiopathic (IPAH) control donors were 3D bioprinted mimic adventitia. These biomaterials initially soft, like healthy then stiffened using light vessel PAH. models showed stiffening microenvironment around IPAH hPAAFs led hPAAF activation. On both protein gene-expression levels, cellular activation markers significantly samples highest patient-derived cells. Treatment with selective receptor modulator reduced expression markers, demonstrating one response mediated by vasculature, validating drugs currently clinical trials could evaluated sex-specific models.

Language: Английский

Citations

0
Female Fibroblast Activation Is Estrogen-Mediated in Sex-Specific 3D-Bioprinted Pulmonary Artery Adventitia Models DOI

Mikala C. Mueller,

Rachel Blomberg, Alicia E. Tanneberger

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Pulmonary arterial hypertension (PAH) is a form of pulmonary vascular disease characterized by scarring the small blood vessels that results in reduced flow and increased pressure lungs. Over time, this increase causes damage to heart. Idiopathic (IPAH) impacts male female patients differently, with showing higher susceptibility (4:1 female-to-male ratio) but experiencing longer survival rates postdiagnosis compared patients. This complex sex dimorphism known as estrogen paradox. Prior studies suggest signaling may be pathologic vasculature protective heart, yet mechanisms underlying these differences IPAH remain unclear. Many previous PAH relied on cells or undisclosed origin for vitro modeling. Here, we present dynamic, three-dimensional (3D)-bioprinted model incorporating circulating hormones from specifically study how respond changes microenvironmental stiffness hormone cellular level. Poly(ethylene glycol)-α methacrylate (PEGαMA)-based hydrogels containing human artery adventitia fibroblasts (hPAAFs) control donors were 3D bioprinted mimic adventitia. These biomaterials initially soft, like healthy vessels, then stiffened using light vessel PAH. 3D-bioprinted models showed stiffening microenvironment around hPAAFs led hPAAF activation. On both protein gene-expression levels, activation markers significantly samples highest patient-derived cells. Treatment selective receptor modulator, which currently clinical trials treatment, expression markers, demonstrating one response mediated vasculature. utility sex-specific, preclinical drug discovery validation.

Language: Английский

Citations

0
Transcriptomic analysis of SEL1L and HRD1 knockout cell lines reveals multifaceted roles of SEL1L beyond the ER quality control DOI Creative Commons
Sally Badawi,

Nesrin Gariballa,

Praseetha Kizhakkedath

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

Abstract The endoplasmic reticulum (ER) orchestrates major cellular processes, including protein synthesis, folding, assembly and degradation, to maintain proteostasis. Central these processes are highly stringent quality control machineries like the ER-associated degradation (ERAD). Key players in ERAD include HRD1 SEL1L, which target misfolded proteins for ubiquitination facilitate their retro-translocation cytosol. Bi-allelic loss-of-function of SEL1L is considered lethal, with hypomorphic variants linked human diseases, neurodevelopmental disorders. Despite well-known roles, a comprehensive transcriptomic characterization bi-allelic loss has been lacking. In this study, we employed CRISPR/Cas9 generate HRD1-KO SEL1L-KO HEK293 cell models. Through differential gene expression analysis co-expression network construction, identified hub genes novel regulatory networks. cells displayed enrichment solely ER-related suggesting its specific role ER control. Conversely, exhibited broader impact, affecting mitochondrial function, ERAD-ribosomal interactions, ER-Golgi transport, Wnt signaling pathway. These results highlight distinct roles ERAD. By unraveling whole transcriptome our study sheds light on potential involvement diverse potentially enhancing understanding disease mechanisms.

Language: Английский

Citations

0
A New Rat Model of Sacral Cord Injury Producing a Neurogenic Bladder and Its Functional and Mechanistic Studies DOI Creative Commons
Kaiping Bai, Yanping Hou, Zhiyuan Zhang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1141 - 1141

Published: Sept. 9, 2024

Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI better understand disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation groups. The group underwent sacral injury, while did not. Urodynamic histological assessments conducted at various intervals (1, 2, 3, 4, 6 weeks) post-injury elucidate process. examinations revealed significant compared group, stabilizing around 3–4 weeks post-injury. Histological examination, including hematoxylin–eosin Masson’s trichrome staining, correlated these functional microstructural alterations. RNA-seq was performed tissues from identify differentially expressed genes pathways. Selected further analyzed using polymerase chain reaction (PCR). findings indicated pronounced inflammatory response first 2 post-SSCI, progressing fibrosis weeks. In conclusion, this presents reliable, reproducible, straightforward model, providing insights morphological alterations post-SSCI laying groundwork for future therapeutic research.

Language: Английский

Citations

0