Biology subjects

Chauvin, S.

Publications and source records attributed to Chauvin, S..

3 recordsLinked to original sources

bioRxiv2026

A cilia-dependent inflammatory programme links bacterial detection to kidney disease

The primary cilium is a microtubule-based sensory organelle projecting from the plasma membrane of most mammalian cells. Genetic defects in ciliary components cause chronic kidney disease (CKD) characterized by heightened production of inflammatory and fibrogenic mediators by tubular epithelial cells. Yet, whether this reflects a physiological role of the primary cilium remains unknown. Here, we show that primary cilia on kidney tubular cells bind uropathogenic Escherichia coli and, in response to bacterial components, initiate a fibro-inflammatory program reminiscent of CKD. Integrating single-cell transcriptomics with conditional mouse models, we observed that epithelial cilia orchestrate a similar fibro-inflammatory response in the absence of infection during CKD. This convergence reveals a shared cilia-dependent signalling axis governing both host-pathogen responses and CKD progression. Mechanistically, cilia ablation selectively impairs tubular responses to ADP-heptose, a pathogen-associated molecular pattern that activates NF-{kappa}B via the cytosolic innate immune receptor ALPK1. In human kidney organoids, ADP-heptose induces robust fibro-inflammation, and genetic or pharmacological inhibition of ALPK1 attenuates this response in a rodent CKD model. Together, these findings identify primary cilia as central orchestrators of a fibro-inflammatory program linking pathogen detection to kidney disease progression.

physiology↗

bioRxiv2025

Decoding the pituitary gonadotrope regulatory architecture governing the preovulatory surge in vivo

Despite the global burden of female infertility, the molecular control of ovulation remains unclear. Pituitary gonadotropes tune hormonal output to regulate ovarian function, yet the molecular mechanisms that control their function during the sexual cycle remain poorly understood. Using state-of-the-art single-nucleus multiomic profiling of the female rat pituitary across the estrus cycle, we uncover unexpected cyclic epigenetic and transcriptional remodelling in gonadotrope cells, particularly during the preovulatory surge. This plasticity is driven by a biphasic gene regulatory network switch that orchestrates large-scale reorganisation of the secretory machinery. We further demonstrate that, contrary to the prevailing model, the LH surge does not depend on Lhb transcriptional upregulation. Instead, the FSH surge arises from dynamic Fshb transcription mediated by a complex combination of newly identified enhancers and key transcription factors. Overall, our findings define a new molecular framework for gonadotropin surge regulation and provide a foundational resource for understanding female reproductive disorders.

physiology↗

bioRxiv2024

Preclinical evaluation of pharmacological inhibition of SIRT1 on the growth of tumoral and metastatic granulosa cells

BackgroundClinical management of patients with recurrent ovarian granulosa cell tumor (GCT) remains poor. Sirtuin-1 (SIRT1), a deacetylase enzyme involved in the regulation of tumor growth and metastasis, may represent a therapeutic target due to the availability of selective pharmacological inhibitors with minimal toxicity. MethodsWe assessed the possible overexpression of SIRT1 during tumorigenesis by Western blot and immunohistochemistry. We tested the effects of SIRT1 inhibition by EX-527 on growth, proliferation, death, migration and gene expression by RNA sequencing and RT-qPCR in vitro on three GCT cell lines (AT29, KGN, COV434). Tumor growth in response to EX-527 treatment was examined in nude mice carrying subcutaneous GCT cell grafts using an electronic caliper and in GCT of AT83 mice by 3D ultrasound imaging system. ResultsSIRT1 abundance increased during tumorigenesis. In vitro treatment with EX-527 efficiently reduced cell growth, either by inducing apoptosis or by inhibiting proliferation. EX-527 induced alterations in pathways driven by mTOR, Myc and E2F, and in pathways controlling cell metabolism and oxidative stress. The administration of this treatment for 4 weeks efficiently reduced tumor progression in vivo. ConclusionsOur study reveals a new therapeutic potential of SIRT1 targeting as a treatment option for patients with recurrent GCT.

cancer biology↗